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Journal of Immunology Research
Volume 2017, Article ID 8193932, 16 pages
https://doi.org/10.1155/2017/8193932
Review Article

The Controversial C5a Receptor C5aR2: Its Role in Health and Disease

Core Research Laboratory, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, China

Correspondence should be addressed to Ke Li; nc.ude.utjx.liam@il.ek

Received 13 March 2017; Accepted 11 May 2017; Published 15 June 2017

Academic Editor: Ethan M. Shevach

Copyright © 2017 Ting Zhang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. D. Ricklin, E. S. Reis, and J. D. Lambris, “Complement in disease: a defence system turning offensive,” Nature Reviews. Nephrology, vol. 12, no. 7, pp. 383–401, 2016. View at Publisher · View at Google Scholar · View at Scopus
  2. A. Klos, E. Wende, K. J. Wareham, and P. N. Monk, “International Union of Basic and Clinical Pharmacology. [corrected]. LXXXVII. Complement peptide C5a, C4a, and C3a receptors,” Pharmacological Reviews, vol. 65, no. 1, pp. 500–543, 2013. View at Google Scholar
  3. D. C. Mastellos, R. A. Deangelis, and J. D. Lambris, “Complement-triggered pathways orchestrate regenerative responses throughout phylogenesis,” Seminars in Immunology, vol. 25, no. 1, pp. 29–38, 2013. View at Publisher · View at Google Scholar · View at Scopus
  4. E. S. Reis, H. Chen, G. Sfyroera et al., “C5a receptor-dependent cell activation by physiological concentrations of desarginated C5a: insights from a novel label-free cellular assay,” Journal of Immunology, vol. 189, no. 10, pp. 4797–4805, 2012. View at Publisher · View at Google Scholar · View at Scopus
  5. A. Klos, A. J. Tenner, K. O. Johswich, R. R. Ager, E. S. Reis, and J. Kohl, “The role of the anaphylatoxins in health and disease,” Molecular Immunology, vol. 46, no. 14, pp. 2753–2766, 2009. View at Publisher · View at Google Scholar · View at Scopus
  6. Q. Peng, K. Li, L. A. Smyth et al., “C3a and C5a promote renal ischemia-reperfusion injury,” Journal of the American Society of Nephrology, vol. 23, no. 9, pp. 1474–1485, 2012. View at Publisher · View at Google Scholar · View at Scopus
  7. D. Rittirsch, M. A. Flierl, B. A. Nadeau et al., “Functional roles for C5a receptors in sepsis,” Nature Medicine, vol. 14, no. 5, pp. 551–557, 2008. View at Publisher · View at Google Scholar · View at Scopus
  8. E. Shagdarsuren, K. Bidzhekov, S. F. Mause et al., “C5a receptor targeting in neointima formation after arterial injury in atherosclerosis-prone mice,” Circulation, vol. 122, no. 10, pp. 1026–1036, 2010. View at Publisher · View at Google Scholar · View at Scopus
  9. M. M. Markiewski and J. D. Lambris, “Unwelcome complement,” Cancer Research, vol. 69, no. 16, p. 6367, 2009. View at Publisher · View at Google Scholar · View at Scopus
  10. D. K. Lee, S. R. George, R. Cheng et al., “Identification of four novel human G protein-coupled receptors expressed in the brain,” Brain Research. Molecular Brain Research, vol. 86, no. 1-2, pp. 13–22, 2001. View at Publisher · View at Google Scholar · View at Scopus
  11. M. Ohno, T. Hirata, M. Enomoto, T. Araki, H. Ishimaru, and T. A. Takahashi, “A putative chemoattractant receptor, C5L2, is expressed in granulocyte and immature dendritic cells, but not in mature dendritic cells,” Molecular Immunology, vol. 37, no. 8, pp. 407–412, 2000. View at Publisher · View at Google Scholar · View at Scopus
  12. S. A. Cain and P. N. Monk, “The orphan receptor C5L2 has high affinity binding sites for complement fragments C5a and C5a des-Arg(74),” The Journal of Biological Chemistry, vol. 277, no. 9, pp. 7165–7169, 2002. View at Publisher · View at Google Scholar · View at Scopus
  13. S. Okinaga, D. Slattery, A. Humbles et al., “C5L2, a nonsignaling C5A binding protein,” Biochemistry, vol. 42, no. 31, pp. 9406–9415, 2003. View at Publisher · View at Google Scholar · View at Scopus
  14. V. Gavrilyuk, S. Kalinin, B. S. Hilbush et al., “Identification of complement 5a-like receptor (C5L2) from astrocytes: characterization of anti-inflammatory properties,” Journal of Neurochemistry, vol. 92, no. 5, pp. 1140–1149, 2005. View at Publisher · View at Google Scholar · View at Scopus
  15. C. Gerard, L. Bao, O. Orozco, M. Pearson, D. Kunz, and N. P. Gerard, “Structural diversity in the extracellular faces of peptidergic G-protein-coupled receptors. Molecular cloning of the mouse C5a anaphylatoxin receptor,” Journal of Immunology, vol. 149, no. 8, pp. 2600–2606, 1992. View at Google Scholar
  16. M. Farzan, C. E. Schnitzler, N. Vasilieva et al., “Sulfated tyrosines contribute to the formation of the C5a docking site of the human C5a anaphylatoxin receptor,” The Journal of Experimental Medicine, vol. 193, no. 9, pp. 1059–1066, 2001. View at Publisher · View at Google Scholar · View at Scopus
  17. H. Gao, T. A. Neff, R. F. Guo et al., “Evidence for a functional role of the second C5a receptor C5L2,” The FASEB Journal, vol. 19, no. 8, pp. 1003–1005, 2005. View at Publisher · View at Google Scholar · View at Scopus
  18. A. M. Scola, K. O. Johswich, B. P. Morgan, A. Klos, and P. N. Monk, “The human complement fragment receptor, C5L2, is a recycling decoy receptor,” Molecular Immunology, vol. 46, no. 6, pp. 1149–1162, 2009. View at Publisher · View at Google Scholar · View at Scopus
  19. R. He, D. D. Browning, and R. D. Ye, “Differential roles of the NPXXY motif in formyl peptide receptor signaling,” Journal of Immunology, vol. 166, no. 6, pp. 4099–4105, 2001. View at Publisher · View at Google Scholar
  20. A. M. Scola, A. Higginbottom, L. J. Partridge et al., “The role of the N-terminal domain of the complement fragment receptor C5L2 in ligand binding,” The Journal of Biological Chemistry, vol. 282, no. 6, pp. 3664–3671, 2007. View at Publisher · View at Google Scholar · View at Scopus
  21. D. E. Croker, P. N. Monk, R. Halai et al., “Discovery of functionally selective C5aR2 ligands: novel modulators of C5a signalling,” Immunology and Cell Biology, vol. 94, no. 8, pp. 787–795, 2016. View at Publisher · View at Google Scholar · View at Scopus
  22. D. E. Croker, R. Halai, G. Kaeslin et al., “C5a2 can modulate ERK1/2 signaling in macrophages via heteromer formation with C5a1 and beta-arrestin recruitment,” Immunology and Cell Biology, vol. 92, no. 7, pp. 631–639, 2014. View at Publisher · View at Google Scholar · View at Scopus
  23. D. E. Croker, R. Halai, D. P. Fairlie, and M. A. Cooper, “C5a, but not C5a-des Arg, induces upregulation of heteromer formation between complement C5a receptors C5aR and C5L2,” Immunology and Cell Biology, vol. 91, no. 10, pp. 625–633, 2013. View at Publisher · View at Google Scholar · View at Scopus
  24. D. Kalant, S. A. Cain, M. Maslowska, A. D. Sniderman, K. Cianflone, and P. N. Monk, “The chemoattractant receptor-like protein C5L2 binds the C3a des-Arg77/acylation-stimulating protein,” The Journal of Biological Chemistry, vol. 278, no. 13, pp. 11123–11129, 2003. View at Publisher · View at Google Scholar · View at Scopus
  25. D. Kalant, R. MacLaren, W. Cui et al., “C5L2 is a functional receptor for acylation-stimulating protein,” The Journal of Biological Chemistry, vol. 280, no. 25, pp. 23936–23944, 2005. View at Publisher · View at Google Scholar · View at Scopus
  26. K. Johswich, M. Martin, J. Thalmann, C. Rheinheimer, P. N. Monk, and A. Klos, “Ligand specificity of the anaphylatoxin C5L2 receptor and its regulation on myeloid and epithelial cell lines,” The Journal of Biological Chemistry, vol. 281, no. 51, pp. 39088–39095, 2006. View at Publisher · View at Google Scholar · View at Scopus
  27. T. Crass, R. S. Ames, H. M. Sarau et al., “Chimeric receptors of the human C3a receptor and C5a receptor (CD88),” The Journal of Biological Chemistry, vol. 274, no. 13, pp. 8367–8370, 1999. View at Publisher · View at Google Scholar · View at Scopus
  28. I. Murray, R. A. Parker, T. G. Kirchgessner et al., “Functional bioactive recombinant acylation stimulating protein is distinct from C3a anaphylatoxin,” Journal of Lipid Research, vol. 38, no. 12, pp. 2492–2501, 1997. View at Google Scholar
  29. W. Cui, M. Lapointe, D. Gauvreau, D. Kalant, and K. Cianflone, “Recombinant C3adesArg/acylation stimulating protein (ASP) is highly bioactive: a critical evaluation of C5L2 binding and 3T3-L1 adipocyte activation,” Molecular Immunology, vol. 46, no. 16, pp. 3207–3217, 2009. View at Publisher · View at Google Scholar · View at Scopus
  30. C. Wei, M. Simaan, S. Laporte, R. Lodge, and K. Cianflone, “C5a- and ASP-mediated C5L2 activation, endocytosis and recycling are lost in S323I-C5L2 mutation,” Molecular Immunology, vol. 46, no. 15, pp. 3086–3098, 2009. View at Google Scholar
  31. P. Poursharifi, M. Lapointe, D. Pétrin et al., “C5L2 and C5aR interaction in adipocytes and macrophages: insights into adipoimmunology,” Cellular Signalling, vol. 25, no. 4, pp. 910–918, 2013. View at Publisher · View at Google Scholar · View at Scopus
  32. W. Cui, S. Paglialunga, D. Kalant et al., “Acylation-stimulating protein/C5L2-neutralizing antibodies alter triglyceride metabolism in vitro and in vivo,” American Journal of Physiology. Endocrinology & Metabolism, vol. 293, no. 6, p. E1482, 2007. View at Publisher · View at Google Scholar · View at Scopus
  33. C. E. Bamberg, C. R. Mackay, H. Lee et al., “The C5a receptor (C5aR) C5L2 is a modulator of C5aR-mediated signal transduction,” The Journal of Biological Chemistry, vol. 285, no. 10, pp. 7633–7644, 2010. View at Publisher · View at Google Scholar · View at Scopus
  34. N. P. Gerard, B. Lu, P. Liu et al., “An anti-inflammatory function for the complement anaphylatoxin C5a-binding protein, C5L2,” The Journal of Biological Chemistry, vol. 280, no. 48, pp. 39677–39680, 2005. View at Publisher · View at Google Scholar · View at Scopus
  35. K. Francis, B. M. Lewis, P. N. Monk, and J. Ham, “Complement C5a receptors in the pituitary gland: expression and function,” The Journal of Endocrinology, vol. 199, no. 3, pp. 417–424, 2008. View at Publisher · View at Google Scholar · View at Scopus
  36. M. Wysoczynski, M. Kucia, J. Ratajczak, and M. Z. Ratajczak, “Cleavage fragments of the third complement component (C3) enhance stromal derived factor-1 (SDF-1)-mediated platelet production during reactive postbleeding thrombocytosis,” Leukemia, vol. 21, no. 5, pp. 973–982, 2007. View at Publisher · View at Google Scholar · View at Scopus
  37. M. B. van Werkhoven, J. Damman, M. R. Daha et al., “Novel insights in localization and expression levels of C5aR and C5L2 under native and post-transplant conditions in the kidney,” Molecular Immunology, vol. 53, no. 3, pp. 237–245, 2013. View at Publisher · View at Google Scholar · View at Scopus
  38. Z. A. Kopp, U. Jain, J. Van Limbergen, and A. W. Stadnyk, “Do antimicrobial peptides and complement collaborate in the intestinal mucosa?” Frontiers in Immunology, vol. 6, p. 17, 2015. View at Publisher · View at Google Scholar · View at Scopus
  39. Q. Cao, S. M. McIsaac, and A. W. Stadnyk, “Human colonic epithelial cells detect and respond to C5a via apically expressed C5aR through the ERK pathway,” American Journal of Physiology. Cell Physiology, vol. 302, no. 12, pp. C1731–C1740, 2012. View at Google Scholar
  40. E. Apostolidou, K. Kambas, A. Chrysanthopoulou et al., “Genetic analysis of C5a receptors in neutrophils from patients with familial Mediterranean fever,” Molecular Biology Reports, vol. 39, no. 5, pp. 5503–5510, 2012. View at Publisher · View at Google Scholar · View at Scopus
  41. Y. G. C. A. Sabio, N. Yokobori, J. I. Basile et al., “C5aR contributes to the weak Th1 profile induced by an outbreak strain of Mycobacterium tuberculosis,” Tuberculosis (Edinburgh, Scotland), vol. 103, pp. 16–23, 2017. View at Publisher · View at Google Scholar
  42. T. M. Woodruff, K. J. Costantini, J. W. Crane et al., “The complement factor C5a contributes to pathology in a rat model of amyotrophic lateral sclerosis,” Journal of Immunology, vol. 181, no. 12, pp. 8727–8734, 2008. View at Publisher · View at Google Scholar
  43. T. M. Woodruff, J. W. Crane, L. M. Proctor et al., “Therapeutic activity of C5a receptor antagonists in a rat model of neurodegeneration,” The FASEB Journal, vol. 20, no. 9, pp. 1407–1417, 2006. View at Publisher · View at Google Scholar · View at Scopus
  44. I. Farkas, M. Sárvári, M. Aller et al., “Estrogen receptor α and β differentially mediate C5aR agonist evoked Ca2+-influx in neurons through L-type voltage-gated Ca2+ channels,” Neurochemistry International, vol. 60, no. 6, pp. 631–639, 2012. View at Publisher · View at Google Scholar · View at Scopus
  45. T. M. Woodruff, R. R. Ager, A. J. Tenner, P. G. Noakes, and S. M. Taylor, “The role of the complement system and the activation fragment C5a in the central nervous system,” Neuromolecular Medicine, vol. 12, no. 2, pp. 179–192, 2010. View at Publisher · View at Google Scholar · View at Scopus
  46. M. I. Fonseca, S. O. McGuire, S. E. Counts, and A. J. Tenner, “Complement activation fragment C5a receptors, CD88 and C5L2, are associated with neurofibrillary pathology,” Journal of Neuroinflammation, vol. 10, p. 25, 2013. View at Publisher · View at Google Scholar · View at Scopus
  47. P. J. C. Biggins, F. H. Brennan, S. M. Taylor, T. M. Woodruff, and M. J. Ruitenberg, “The alternative receptor for complement component 5a, C5aR2, conveys neuroprotection in traumatic spinal cord injury,” Journal of Neurotrauma, 2017. View at Publisher · View at Google Scholar
  48. A. N. Spaan, T. Henry, and Willemien J. M. van Rooijen, et al., “The staphylococcal toxin Panton-Valentine leukocidin targets human C5a receptors,” Cell Host & Microbe, vol. 13, no. 5, pp. 584–594, 2013. View at Publisher · View at Google Scholar · View at Scopus
  49. R. Li, L. G. Coulthard, M. C. Wu, S. M. Taylor, and T. M. Woodruff, “C5L2: a controversial receptor of complement anaphylatoxin, C5a,” The FASEB Journal, vol. 27, no. 3, pp. 855–864, 2013. View at Publisher · View at Google Scholar · View at Scopus
  50. S. A. Horst, A. Itzek, A. Klos, A. Beineke, and E. Medina, “Differential contributions of the complement anaphylotoxin receptors C5aR1 and C5aR2 to the early innate immune response against Staphylococcus aureus infection,” Pathogens (Basel, Switzerland), vol. 4, no. 4, pp. 722–738, 2015. View at Google Scholar
  51. M. Otto, H. Hawlisch, P. N. Monk et al., “C5a mutants are potent antagonists of the C5a receptor (CD88) and of C5L2: position 69 is the locus that determines agonism or antagonism,” The Journal of Biological Chemistry, vol. 279, no. 1, pp. 142–151, 2004. View at Publisher · View at Google Scholar · View at Scopus
  52. K. Bachmaier, E. Guzman, T. Kawamura, X. Gao, and A. B. Malik, “Sphingosine kinase 1 mediation of expression of the anaphylatoxin receptor C5L2 dampens the inflammatory response to endotoxin,” PloS One, vol. 7, no. 2, article e30742, 2012. View at Publisher · View at Google Scholar · View at Scopus
  53. H. Tang, U. Amara, D. Tang, M. A. Barnes, C. McDonald, and L. E. Nagy, “Synergistic interaction between C5a and NOD2 signaling in the regulation of chemokine expression in RAW 264.7 macrophages,” Advances in Bioscience and Biotechnology (Print), vol. 4, no. 8C, pp. 30–37, 2013. View at Google Scholar
  54. G. Arbore, E. E. West, R. Spolski et al., “T helper 1 immunity requires complement-driven NLRP3 inflammasome activity in CD4(+) T cells,” Science, vol. 352, no. 6292, p. aad1210, 2016. View at Publisher · View at Google Scholar · View at Scopus
  55. P. Pundir, C. A. MacDonald, and M. Kulka, “The novel receptor C5aR2 is required for C5a-mediated human mast cell adhesion, migration, and proinflammatory mediator production,” Journal of Immunology, vol. 195, no. 6, pp. 2774–2787, 2015. View at Publisher · View at Google Scholar · View at Scopus
  56. R. Wang, B. Lu, C. Gerard, and N. P. Gerard, “Disruption of the complement anaphylatoxin receptor C5L2 exacerbates inflammation in allergic contact dermatitis,” Journal of Immunology, vol. 191, no. 8, pp. 4001–4009, 2013. View at Publisher · View at Google Scholar · View at Scopus
  57. M. Huber-Lang, J. V. Sarma, D. Rittirsch et al., “Changes in the novel orphan, C5a receptor (C5L2), during experimental sepsis and sepsis in humans,” Journal of Immunology, vol. 174, no. 2, pp. 1104–1110, 2005. View at Google Scholar
  58. A. Vibhuti, K. Gupta, H. Subramanian, Q. Guo, and H. Ali, “Distinct and shared roles of beta-arrestin-1 and beta-arrestin-2 on the regulation of C3a receptor signaling in human mast cells,” PloS One, vol. 6, no. 5, article e19585, 2011. View at Publisher · View at Google Scholar · View at Scopus
  59. S. M. DeWire, S. Ahn, R. J. Lefkowitz, and S. K. Shenoy, “Beta-arrestins and cell signaling,” Annual Review of Physiology, vol. 69, pp. 483–510, 2007. View at Publisher · View at Google Scholar
  60. L. H. Van Lith, J. Oosterom, A. Van Elsas, and G. J. Zaman, “C5a-stimulated recruitment of beta-arrestin2 to the nonsignaling 7-transmembrane decoy receptor C5L2,” Journal of Biomolecular Screening, vol. 14, no. 9, pp. 1067–1075, 2009. View at Publisher · View at Google Scholar · View at Scopus
  61. H. F. Vischer, A. O. Watts, S. Nijmeijer, and R. Leurs, “G protein-coupled receptors: walking hand-in-hand, talking hand-in-hand?” British Journal of Pharmacology, vol. 163, no. 2, pp. 246–260, 2011. View at Publisher · View at Google Scholar · View at Scopus
  62. M. J. Rabiet, E. Huet, and F. Boulay, “The N-formyl peptide receptors and the anaphylatoxin C5a receptors: an overview,” Biochimie, vol. 89, no. 9, p. 1089, 2007. View at Publisher · View at Google Scholar · View at Scopus
  63. M. J. Rabiet, E. Huet, and F. Boulay, “Complement component 5a receptor oligomerization and homologous receptor down-regulation,” The Journal of Biological Chemistry, vol. 283, no. 45, pp. 31038–31046, 2008. View at Publisher · View at Google Scholar · View at Scopus
  64. M. E. Moreno-Fernandez, J. Aliberti, S. Groeneweg, J. Kohl, and C. A. Chougnet, “A novel role for the receptor of the complement cleavage fragment C5a, C5aR1, in CCR5-mediated entry of HIV into macrophages,” AIDS Research and Human Retroviruses, vol. 32, no. 4, pp. 399–408, 2016. View at Publisher · View at Google Scholar · View at Scopus
  65. X. Zhang, I. Schmudde, Y. Laumonnier et al., “A critical role for C5L2 in the pathogenesis of experimental allergic asthma,” Journal of Immunology, vol. 185, no. 11, pp. 6741–6752, 2010. View at Publisher · View at Google Scholar · View at Scopus
  66. J. Selle, Y. Asare, J. Kohncke et al., “Atheroprotective role of C5ar2 deficiency in apolipoprotein E-deficient mice,” Thrombosis and Haemostasis, vol. 114, no. 4, pp. 848–858, 2015. View at Publisher · View at Google Scholar · View at Scopus
  67. W. C. Hsu, F. C. Yang, C. H. Lin, S. L. Hsieh, and N. J. Chen, “C5L2 is required for C5a-triggered receptor internalization and ERK signaling,” Cellular Signalling, vol. 26, no. 7, pp. 1409–1419, 2014. View at Publisher · View at Google Scholar · View at Scopus
  68. N. J. Chen, C. Mirtsos, D. Suh et al., “C5L2 is critical for the biological activities of the anaphylatoxins C5a and C3a,” Nature, vol. 446, no. 7132, pp. 203–207, 2007. View at Publisher · View at Google Scholar · View at Scopus
  69. C. W. Strey, B. Siegmund, S. Rosenblum et al., “Complement and neutrophil function changes after liver resection in humans,” World Journal of Surgery, vol. 33, no. 12, pp. 2635–2643, 2009. View at Publisher · View at Google Scholar · View at Scopus
  70. E. Passante, C. Ehrhardt, H. Sheridan, and N. Frankish, “RBL-2H3 cells are an imprecise model for mast cell mediator release,” Inflammation Research, vol. 58, no. 9, pp. 611–618, 2009. View at Publisher · View at Google Scholar · View at Scopus
  71. M. Bosmann, J. J. Grailer, R. Ruemmler et al., “Extracellular histones are essential effectors of C5aR- and C5L2-mediated tissue damage and inflammation in acute lung injury,” The FASEB Journal, vol. 27, no. 12, pp. 5010–5021, 2013. View at Publisher · View at Google Scholar · View at Scopus
  72. T. Zhang, Y. Lin, K. Wu et al., “C5L2 deficiency protects mice from kidney infection induced by uropathogenic E. coli,” Molecular Immunology, vol. 61, no. 2, pp. 228-229, 2014. View at Google Scholar
  73. F. Poppelaars, M. B. van Werkhoven, J. Kotimaa et al., “Critical role for complement receptor C5aR2 in the pathogenesis of renal ischemia-reperfusion injury,” The FASEB Journal, 2017. View at Publisher · View at Google Scholar
  74. R. Wang, B. Lu, C. Gerard, and N. P. Gerard, “C5L2, the second C5a anaphylatoxin receptor, suppresses LPS-induced acute lung injury,” American Journal of Respiratory Cell and Molecular Biology, vol. 55, no. 5, pp. 657–666, 2016. View at Publisher · View at Google Scholar · View at Scopus
  75. G. Atefi, F. S. Zetoune, T. J. Herron et al., “Complement dependency of cardiomyocyte release of mediators during sepsis,” The FASEB Journal, vol. 25, no. 7, pp. 2500–2508, 2011. View at Publisher · View at Google Scholar · View at Scopus
  76. M. Kalbitz, F. Fattahi, T. J. Herron et al., “Complement destabilizes cardiomyocyte function in vivo after Polymicrobial sepsis and in vitro,” Journal of Immunology, vol. 197, no. 6, pp. 2353–2361, 2016. View at Publisher · View at Google Scholar · View at Scopus
  77. M. Kalbitz, F. Fattahi, J. J. Grailer et al., “Complement-induced activation of the cardiac NLRP3 inflammasome in sepsis,” The FASEB Journal, vol. 30, no. 12, pp. 3997–4006, 2016. View at Publisher · View at Google Scholar · View at Scopus
  78. M. Kalbitz, J. J. Grailer, F. Fattahi et al., “Role of extracellular histones in the cardiomyopathy of sepsis,” The FASEB Journal, vol. 29, no. 5, pp. 2185–2193, 2015. View at Publisher · View at Google Scholar · View at Scopus
  79. M. Bosmann, M. D. Haggadone, F. S. Zetoune, J. V. Sarma, and P. A. Ward, “C5a interaction with both C5aR and C5L2 receptors is required for production of G-CSF during the acute inflammatory response,” European Journal of Immunology, vol. 43, no. 7, pp. 1907–1913, 2013. View at Publisher · View at Google Scholar · View at Scopus
  80. P. A. Ward, “The harmful role of C5a on innate immunity in sepsis,” Journal of Innate Immunity, vol. 2, no. 5, pp. 439–445, 2010. View at Publisher · View at Google Scholar · View at Scopus
  81. M. A. Flierl, D. Rittirsch, A. J. Chen et al., “The complement anaphylatoxin C5a induces apoptosis in adrenomedullary cells during experimental sepsis,” PloS One, vol. 3, no. 7, p. e2560, 2008. View at Publisher · View at Google Scholar · View at Scopus
  82. R. Xu, F. Lin, C. Bao et al., “Complement 5a receptor-mediated neutrophil dysfunction is associated with a poor outcome in sepsis,” Cellular & Molecular Immunology, vol. 13, no. 1, pp. 103–109, 2016. View at Publisher · View at Google Scholar · View at Scopus
  83. G. Hajishengallis and J. D. Lambris, “Crosstalk pathways between toll-like receptors and the complement system,” Trends in Immunology, vol. 31, no. 4, pp. 154–163, 2010. View at Publisher · View at Google Scholar · View at Scopus
  84. M. Wang, J. L. Krauss, H. Domon et al., “Microbial hijacking of complement-toll-like receptor crosstalk,” Science Signaling, vol. 3, no. 109, p. ra11, 2010. View at Publisher · View at Google Scholar · View at Scopus
  85. N. C. Riedemann, R. F. Guo, T. J. Hollmann et al., “Regulatory role of C5a in LPS-induced IL-6 production by neutrophils during sepsis,” The FASEB Journal, vol. 18, no. 2, pp. 370–372, 2004. View at Publisher · View at Google Scholar
  86. A. C. Raby, B. Holst, J. Davies et al., “TLR activation enhances C5a-induced pro-inflammatory responses by negatively modulating the second C5a receptor, C5L2,” European Journal of Immunology, vol. 41, no. 9, pp. 2741–2752, 2011. View at Publisher · View at Google Scholar · View at Scopus
  87. S. Vijayan, Y. Asare, J. Grommes et al., “High expression of C5L2 correlates with high Proinflammatory cytokine expression in advanced human atherosclerotic plaques,” The American Journal of Pathology, vol. 184, no. 7, pp. 2123–2133, 2014. View at Publisher · View at Google Scholar · View at Scopus
  88. H. Xiao, D. J. Dairaghi, J. P. Powers et al., “C5a receptor (CD88) blockade protects against MPO-ANCA GN,” Journal of the American Society of Nephrology, vol. 25, no. 2, pp. 225–231, 2014. View at Publisher · View at Google Scholar · View at Scopus
  89. J. Hao, C. Wang, J. Yuan, M. Chen, and M. H. Zhao, “A pro-inflammatory role of C5L2 in C5a-primed neutrophils for ANCA-induced activation,” PloS One, vol. 8, no. 6, p. e66305, 2013. View at Publisher · View at Google Scholar · View at Scopus
  90. E. Shagdarsuren, K. Bidzhekov, S. Mause et al., “C5a receptor targeting in neointima formation after arterial injury in atherosclerosis-prone mice,” Molecular Immunology, vol. 47, no. 13, p. 2207, 2010. View at Publisher · View at Google Scholar
  91. R. Oksjoki, P. Laine, S. Helske et al., “Receptors for the anaphylatoxins C3a and C5a are expressed in human atherosclerotic coronary plaques,” Atherosclerosis, vol. 195, no. 1, pp. 90–99, 2007. View at Publisher · View at Google Scholar · View at Scopus
  92. A. Hovland, L. Jonasson, P. Garred et al., “The complement system and toll-like receptors as integrated players in the pathophysiology of atherosclerosis,” Atherosclerosis, vol. 241, no. 2, pp. 480–494, 2015. View at Publisher · View at Google Scholar · View at Scopus
  93. J. Patzelt, K. A. L. Mueller, S. Breuning et al., “Expression of anaphylatoxin receptors on platelets in patients with coronary heart disease,” Atherosclerosis, vol. 238, no. 2, pp. 289–295, 2015. View at Publisher · View at Google Scholar · View at Scopus
  94. H. D. Manthey, A. C. Thomas, I. A. Shiels et al., “Complement C5a inhibition reduces atherosclerosis in ApoE−/− mice,” The FASEB Journal, vol. 25, no. 7, pp. 2447–2455, 2011. View at Publisher · View at Google Scholar · View at Scopus
  95. Y. Liu, A. Fisette, M. Lapointe, and K. Cianflone, “C5L2 deficiency enhances development of atherosclerosis in ApoE knockout mice,” Chinese Medicine, vol. 06, no. 01, p. 15, 2015. View at Google Scholar
  96. F. Chmilewsky, I. About, and S. H. Chung, “C5L2 receptor represses brain-derived neurotrophic factor secretion in lipoteichoic acid-stimulated pulp fibroblasts,” Journal of Dental Research, vol. 96, no. 1, pp. 92–99, 2017. View at Publisher · View at Google Scholar
  97. S. He, C. Atkinson, F. Qiao, K. Cianflone, X. Chen, and S. Tomlinson, “A complement-dependent balance between hepatic ischemia/reperfusion injury and liver regeneration in mice,” Journal of Clinical Investigation, vol. 119, no. 8, pp. 2304–2316, 2009. View at Publisher · View at Google Scholar · View at Scopus
  98. M. Honczarenko, B. Lu, A. Nicholsonweller, N. P. Gerard, L. E. Silberstein, and C. Gerard, “C5L2 receptor is not involved in C3a / C3a-desArg-mediated enhancement of bone marrow hematopoietic cell migration to CXCL12,” Leukemia, vol. 19, no. 9, pp. 1684-1685, 2005. View at Google Scholar
  99. G. Arbore and C. Kemper, “A novel “complement-metabolism-inflammasome axis” as a key regulator of immune cell effector function,” European Journal of Immunology, vol. 46, no. 7, pp. 1563–1573, 2016. View at Publisher · View at Google Scholar · View at Scopus
  100. M. Kolev, S. Dimeloe, G. Le Friec et al., “Complement regulates nutrient influx and metabolic reprogramming during Th1 cell responses,” Immunity, vol. 42, no. 6, pp. 1033–1047, 2015. View at Publisher · View at Google Scholar · View at Scopus
  101. J. Phieler, R. Garcia-Martin, J. D. Lambris, and T. Chavakis, “The role of the complement system in metabolic organs and metabolic diseases,” Seminars in Immunology, vol. 25, no. 1, pp. 47–53, 2013. View at Publisher · View at Google Scholar · View at Scopus
  102. A. Fisette and K. Cianflone, “The ASP and C5L2 pathway: another bridge between inflammation and metabolic homeostasis,” Clinical Lipidology, vol. 5, no. 3, pp. 367–377, 2010. View at Publisher · View at Google Scholar · View at Scopus
  103. K. Johswich and A. Klos, “C5L2—an anti-inflammatory molecule or a receptor for acylation stimulating protein (C3a-desArg)?” Advances in Experimental Medicine & Biology, vol. 598, no. 598, pp. 159–150, 2007. View at Google Scholar
  104. Y. Wen, H. Wang, R. J. Wu, H. Lu, and K. Cianflone, “Palmitate and oleate induction of acylation stimulating protein resistance in 3T3-L1 adipocytes and preadipocytes,” Journal of Cellular Biochemistry, vol. 104, no. 2, pp. 391–401, 2008. View at Publisher · View at Google Scholar · View at Scopus
  105. M. Maslowska, H. Legakis, F. Assadi, and K. Cianflone, “Targeting the signaling pathway of acylation stimulating protein,” Journal of Lipid Research, vol. 47, no. 3, p. 643, 2006. View at Publisher · View at Google Scholar · View at Scopus
  106. S. Paglialunga, P. Schrauwen, C. Roy et al., “Reduced adipose tissue triglyceride synthesis and increased muscle fatty acid oxidation in C5L2 knockout mice,” Journal of Endocrinology, vol. 194, no. 2, pp. 293–304, 2007. View at Publisher · View at Google Scholar · View at Scopus
  107. Y. Wen, H. Wang, R. Maclaren, H. Lu, X. F. Hu, and K. Cianflone, “Sex steroid hormones induce acylation stimulating protein resistance in 3T3-L1 adipocytes,” Journal of Cellular Biochemistry, vol. 105, no. 2, pp. 404–413, 2008. View at Publisher · View at Google Scholar · View at Scopus
  108. Y. Wen, H. W. Wang, X. F. Hu et al., “Role of progesterone in acylation stimulating protein-receptor C5L2 pathway in adipocytes and preadipocytes,” Zhonghua Yi Xue Za Zhi, vol. 88, no. 2, pp. 114–118, 2008. View at Google Scholar
  109. R. Maclaren, D. Kalant, and K. Cianflone, “The ASP receptor C5L2 is regulated by metabolic hormones associated with insulin resistance,” Biochemistry and Cell Biology, vol. 85, no. 1, pp. 11–21, 2007. View at Publisher · View at Google Scholar · View at Scopus
  110. S. Paglialunga, A. Fisette, M. Munkonda, Y. Gao, D. Richard, and K. Cianflone, “The effects of acylation stimulating protein supplementation VS antibody neutralization on energy expenditure in wildtype mice,” BMC Physiology, vol. 10, no. 1, p. 4, 2010. View at Publisher · View at Google Scholar · View at Scopus
  111. C. Roy, S. Paglialunga, G. Schaart et al., “Relationship of C5L2 receptor to skeletal muscle substrate utilization,” PloS One, vol. 8, no. 2, p. e57494, 2013. View at Publisher · View at Google Scholar · View at Scopus
  112. A. Fisette, M. N. Munkonda, K. Oikonomopoulou, S. Paglialunga, J. D. Lambris, and K. Cianflone, “C5L2 receptor disruption enhances the development of diet-induced insulin resistance in mice,” Immunobiology, vol. 218, no. 1, pp. 127–133, 2013. View at Publisher · View at Google Scholar · View at Scopus
  113. D. Gauvreau, A. Gupta, A. Fisette, F. Q. Tom, and K. Cianflone, “Deficiency of C5L2 increases macrophage infiltration and alters adipose tissue function in mice,” PloS One, vol. 8, no. 4, p. e60795, 2013. View at Publisher · View at Google Scholar · View at Scopus
  114. M. Marcil, H. Vu, W. Cui et al., “Identification of a novel C5L2 variant (S323I) in a French Canadian family with familial combined hyperlipemia,” Arteriosclerosis Thrombosis & Vascular Biology, vol. 26, no. 7, p. 1619, 2006. View at Publisher · View at Google Scholar · View at Scopus
  115. H. Jiang, X. Liu, D. Wang et al., “Association of acylation-stimulating protein and receptor gene polymorphisms with coronary heart disease in Han and Hui populations,” International Journal of Clinical & Experimental Medicine, vol. 8, no. 10, p. 18779, 2015. View at Google Scholar
  116. L. Qu, X. Jin, L. Li, S. Li, and H. Xie, “A novel mutation in C5L2 gene was associated with hyperlipidemia and retinitis pigmentosa in a Chinese family,” Lipids in Health & Disease, vol. 13, no. 1, p. 75, 2014. View at Publisher · View at Google Scholar · View at Scopus
  117. K. K. Alharbi, I. A. Khan, and R. Syed, “Circulating C5L2 gene polymorphism is associated with type 2 diabetes mellitus in Saudi population,” Molecular Biology Reports, vol. 40, no. 11, pp. 6323–6327, 2013. View at Publisher · View at Google Scholar · View at Scopus
  118. Y. Zheng, Y. Ma, Y. Yang, F. Liu, and X. Xiang, “Relationship between a novel polymorphism of the C5L2 gene and coronary artery disease,” PloS One, vol. 6, no. 6, p. e20984, 2011. View at Publisher · View at Google Scholar · View at Scopus
  119. Y. Y. Zheng, X. Xie, Y. T. Ma et al., “Association of C5L2 genetic polymorphisms with coronary artery disease in a Han population in Xinjiang, China,” Oncotarget, vol. 8, no. 5, pp. 8590–8596, 2017. View at Publisher · View at Google Scholar
  120. P. Poursharifi, M. Lapointe, A. Fisette et al., “C5aR and C5L2 act in concert to balance immunometabolism in adipose tissue,” Molecular & Cellular Endocrinology, vol. 382, no. 1, p. 325, 2014. View at Publisher · View at Google Scholar · View at Scopus
  121. P. Poursharifi, R. Rezvani, A. Gupta et al., “Association of immune and metabolic receptors C5aR and C5L2 with adiposity in women,” Mediators of Inflammation, vol. 2014, no. 1, p. 413921, 2013. View at Google Scholar
  122. R. Rezvani, J. Smith, M. Lapointe, P. Marceau, A. Tchernof, and K. Cianflone, “Complement receptors C5aR and C5L2 are associated with metabolic profile, sex hormones, and liver enzymes in obese women pre- and postbariatric surgery,” Journal of Obesity, vol. 2014, Article ID 383102, 2014. View at Google Scholar
  123. A. C. Raby, C. S. Colmont, A. Kift-Morgan et al., “Toll-like receptors 2 and 4 are potential therapeutic targets in peritoneal dialysis-associated fibrosis,” Journal of the American Society of Nephrology, vol. 28, no. 2, pp. 461–478, 2017. View at Publisher · View at Google Scholar
  124. H. Kim, L. K. Erdman, Z. Lu et al., “Functional roles for C5a and C5aR but not C5L2 in the pathogenesis of human and experimental cerebral malaria,” Infection & Immunity, vol. 82, no. 1, pp. 371–379, 2013. View at Publisher · View at Google Scholar · View at Scopus
  125. S. A. Horst, A. Itzek, A. Klos, A. Beineke, and E. Medina, “Differential contributions of the complement anaphylotoxin receptors C5aR1 and C5aR2 to the early innate immune response against Staphylococcus aureus infection,” Pathogens, vol. 4, no. 4, pp. 722–738, 2015. View at Publisher · View at Google Scholar
  126. A. L. Conroy, K. L. Silver, K. Zhong et al., “Complement activation and the resulting placental vascular insufficiency drives fetal growth restriction associated with placental malaria,” Cell Host & Microbe, vol. 13, no. 2, pp. 215–226, 2013. View at Publisher · View at Google Scholar · View at Scopus
  127. P. N. Monk, M. L. Bellows-Peterson, J. Smadbeck et al., “De novo protein design of agonists and antagonists of C5a receptors,” Immunobiology, vol. 217, no. 11, pp. 1162-1163, 2012. View at Publisher · View at Google Scholar
  128. A. N. Spaan, A. Schiepers, C. J. de Haas et al., “Differential interaction of the staphylococcal toxins Panton-Valentine leukocidin and γ-hemolysin CB with human C5a receptors,” Journal of Immunology, vol. 195, no. 3, p. 1034, 2015. View at Publisher · View at Google Scholar · View at Scopus
  129. A. N. Spaan, M. Vrieling, P. Wallet et al., “The staphylococcal toxins γ-haemolysin AB and CB differentially target phagocytes by employing specific chemokine receptors,” Nature Communications, vol. 5, pp. 5438–5438, 2013. View at Google Scholar
  130. P. N. Monk, A. M. Scola, P. Madala, and D. P. Fairlie, “Function, structure and therapeutic potential of complement C5a receptors,” British Journal of Pharmacology, vol. 152, no. 4, p. 429, 2007. View at Google Scholar
  131. H. Lee, P. L. Whitfeld, and C. R. Mackay, “Receptors for complement C5a. The importance of C5aR and the enigmatic role of C5L2,” Immunology & Cell Biology, vol. 86, no. 2, pp. 153–160, 2008. View at Publisher · View at Google Scholar · View at Scopus
  132. M. K. Liszewski, M. Kolev, G. Le Friec et al., “Intracellular complement activation sustains T cell homeostasis and mediates effector differentiation,” Immunity, vol. 39, no. 6, pp. 1143–1157, 2013. View at Publisher · View at Google Scholar · View at Scopus
  133. J. V. Sarma and P. A. Ward, “New developments in C5a receptor signaling,” Cell Health & Cytoskeleton, vol. 4, p. 73, 2012. View at Google Scholar
  134. N. Jia, “Pivotal advance: interconversion between pure chemotactic ligands and chemoattractant/secretagogue ligands of neutrophil C5a receptor by a single amino acid substitution,” Journal of Leukocyte Biology, vol. 87, no. 6, p. 965, 2010. View at Publisher · View at Google Scholar · View at Scopus
  135. H. Nishiura, S. Tanase, Y. Shibuya et al., “S19 ribosomal protein dimer augments metal-induced apoptosis in a mouse fibroblastic cell line by ligation of the C5a receptor,” Journal of Cellular Biochemistry, vol. 94, no. 3, pp. 540–553, 2005. View at Publisher · View at Google Scholar · View at Scopus