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BioMed Research International
Volume 2015, Article ID 747864, 12 pages
http://dx.doi.org/10.1155/2015/747864
Research Article

Isolation and Characterization of Human Lung Lymphatic Endothelial Cells

Bruno Lorusso,1 Angela Falco,1 Denise Madeddu,1 Caterina Frati,1 Stefano Cavalli,1 Gallia Graiani,1 Andrea Gervasi,1 Laura Rinaldi,1 Costanza Lagrasta,2 Davide Maselli,1 Letizia Gnetti,2 Enrico M. Silini,2 Eugenio Quaini,3 Luca Ampollini,4 Paolo Carbognani,4 and Federico Quaini1

1Department of Clinical and Experimental Medicine, University Hospital of Parma, 43126 Parma, Italy
2Department of Biomedical, Biotechnological, and Translational Sciences (S.Bi.Bi.T.), University Hospital of Parma, 43126 Parma, Italy
3Cardiovascular Department, Humanitas Clinical and Research Centre, 20089 Milan, Italy
4Department of Surgical Sciences, University Hospital of Parma, 43126 Parma, Italy

Received 23 October 2014; Revised 24 December 2014; Accepted 12 January 2015

Academic Editor: Themis R. Kyriakides

Copyright © 2015 Bruno Lorusso 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. G. Oliver and M. Detmar, “The rediscovery of the lymphatic system: old and new insights into the development and biological function of the lymphatic vasculature,” Genes & Development, vol. 16, no. 7, pp. 773–783, 2002. View at Publisher · View at Google Scholar · View at Scopus
  2. G. Oliver, “Lymphatic vasculature development,” Nature Reviews Immunology, vol. 4, no. 1, pp. 35–45, 2004. View at Publisher · View at Google Scholar · View at Scopus
  3. G. Oliver and K. Alitalo, “The lymphatic vasculature: recent progress and paradigms,” Annual Review of Cell and Developmental Biology, vol. 21, pp. 457–483, 2005. View at Publisher · View at Google Scholar · View at Scopus
  4. T. Tammela and K. Alitalo, “Lymphangiogenesis: molecular mechanisms and future promise,” Cell, vol. 140, no. 4, pp. 460–476, 2010. View at Publisher · View at Google Scholar · View at Scopus
  5. Z. Jakus, J. P. Gleghorn, D. R. Enis et al., “Lymphatic function is required prenatally for lung inflation at birth,” Journal of Experimental Medicine, vol. 211, no. 5, pp. 815–826, 2014. View at Publisher · View at Google Scholar · View at Scopus
  6. S. Banerji, J. Ni, S.-X. Wang et al., “LYVE-1, a new homologue of the CD44 glycoprotein, is a lymph-specific receptor for hyaluronan,” Journal of Cell Biology, vol. 144, no. 4, pp. 789–801, 1999. View at Publisher · View at Google Scholar · View at Scopus
  7. J. T. Wigle, N. Harvey, M. Detmar et al., “An essential role for Prox1 in the induction of the lymphatic endothelial cell phenotype,” The EMBO Journal, vol. 21, no. 7, pp. 1505–1513, 2002. View at Publisher · View at Google Scholar · View at Scopus
  8. S. Breiteneder-Geleff, A. Soleiman, H. Kowalski et al., “Angiosarcomas express mixed endothelial phenotypes of blood and lymphatic capillaries: podoplanin as a specific marker for lymphatic endothelium,” The American Journal of Pathology, vol. 154, no. 2, pp. 385–394, 1999. View at Publisher · View at Google Scholar · View at Scopus
  9. A. Kaipainen, J. Korhonen, T. Mustonen et al., “Expression of the fms-like tyrosine kinase 4 gene becomes restricted to lymphatic endothelium during development,” Proceedings of the National Academy of Sciences of the United States of America, vol. 92, no. 8, pp. 3566–3570, 1995. View at Publisher · View at Google Scholar · View at Scopus
  10. N. Ferrara, H.-P. Gerber, and J. LeCouter, “The biology of VEGF and its receptors,” Nature Medicine, vol. 9, no. 6, pp. 669–676, 2003. View at Publisher · View at Google Scholar · View at Scopus
  11. M. H. Witte, M. J. Bernas, C. P. Martin, and C. L. Witte, “Lymphangiogenesis and lymphangiodysplasia: from molecular to clinical lymphology,” Microscopy Research and Technique, vol. 55, no. 2, pp. 122–145, 2001. View at Publisher · View at Google Scholar · View at Scopus
  12. T. Bartholin, Vasa Lymphatica in Homine Nuper Inventa, Hafniae Paulli, Copenhagen, Denmark, 1654.
  13. F. Sozio, A. Rossi, E. Weber et al., “Morphometric analysis of intralobular, interlobular and pleural lymphatics in normal human lung,” Journal of Anatomy, vol. 220, no. 4, pp. 396–404, 2012. View at Publisher · View at Google Scholar · View at Scopus
  14. M. Kambouchner and J.-F. Bernaudin, “Intralobular pulmonary lymphatic distribution in normal human lung using D2-40 antipodoplanin immunostaining,” Journal of Histochemistry and Cytochemistry, vol. 57, no. 7, pp. 643–648, 2009. View at Publisher · View at Google Scholar · View at Scopus
  15. D. E. Schraufnagel, “Lung lymphatic anatomy and correlates,” Pathophysiology, vol. 17, no. 4, pp. 337–343, 2010. View at Publisher · View at Google Scholar · View at Scopus
  16. M. P. Pusztaszeri, W. Seelentag, and F. T. Bosman, “Immunohistochemical expression of endothelial markers CD31, CD34, von Willebrand factor, and Fli-1 in normal human tissues,” Journal of Histochemistry and Cytochemistry, vol. 54, no. 4, pp. 385–395, 2006. View at Publisher · View at Google Scholar · View at Scopus
  17. S. El-Chemaly, S. J. Levine, and J. Moss, “Lymphatics in lung disease,” Annals of the New York Academy of Sciences, vol. 1131, pp. 195–202, 2008. View at Publisher · View at Google Scholar · View at Scopus
  18. M. Yamashita, N. Iwama, F. Date et al., “Characterization of lymphangiogenesis in various stages of idiopathic diffuse alveolar damage,” Human Pathology, vol. 40, no. 4, pp. 542–551, 2009. View at Publisher · View at Google Scholar · View at Scopus
  19. R. V. Mandal, E. J. Mark, and R. L. Kradin, “Organizing pneumonia and pulmonary lymphatic architecture in diffuse alveolar damage,” Human Pathology, vol. 39, no. 8, pp. 1234–1238, 2008. View at Publisher · View at Google Scholar · View at Scopus
  20. C. G. Glasgow, S. El-Chemaly, and J. Moss, “Lymphatics in lymphangioleiomyomatosis and idiopathic pulmonary fibrosis,” European Respiratory Review, vol. 21, no. 125, pp. 196–206, 2012. View at Publisher · View at Google Scholar · View at Scopus
  21. S. El-Chemaly, D. Malide, E. Zudaire et al., “Abnormal lymphangiogenesis in idiopathic pulmonary fibrosis with insights into cellular and molecular mechanisms,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 10, pp. 3958–3963, 2009. View at Publisher · View at Google Scholar · View at Scopus
  22. Y. Zeng, K. Opeskin, J. Goad, and E. D. Williams, “Tumor-induced activation of lymphatic endothelial cells via vascular endothelial growth factor receptor-2 is critical for prostate cancer lymphatic metastasis,” Cancer Research, vol. 66, no. 19, pp. 9566–9575, 2006. View at Publisher · View at Google Scholar · View at Scopus
  23. S. Norgall, M. Papoutsi, J. Rössler, L. Schweigerer, J. Wilting, and H. A. Weich, “Elevated expression of VEGFR-3 in lymphatic endothelial cells from lymphangiomas,” BMC Cancer, vol. 7, article 105, 2007. View at Publisher · View at Google Scholar · View at Scopus
  24. E. Garrafa, L. Trainini, A. Benetti et al., “Isolation, purification, and heterogeneity of human lymphatic endothelial cells from different tissues,” Lymphology, vol. 38, no. 4, pp. 159–166, 2005. View at Google Scholar · View at Scopus
  25. S. Fiorentini, A. Luganini, V. Dell'Oste et al., “Human cytomegalovirus productively infects lymphatic endothelial cells and induces a secretome that promotes angiogenesis and lymphangiogenesis through interleukin-6 and granulocyte-macrophage colony-stimulating factor,” Journal of General Virology, vol. 92, no. 3, pp. 650–660, 2011. View at Publisher · View at Google Scholar · View at Scopus
  26. J. D. Catravas, C. Snead, C. Dimitropoulou et al., “Harvesting, identification and barrier function of human lung microvascular endothelial cells,” Vascular Pharmacology, vol. 52, no. 5-6, pp. 175–181, 2010. View at Publisher · View at Google Scholar · View at Scopus
  27. S. A. A. Comhair, W. Xu, L. Mavrakis, M. A. Aldred, K. Asosingh, and S. C. Erzurum, “Human primary lung endothelial cells in culture,” American Journal of Respiratory Cell and Molecular Biology, vol. 46, no. 6, pp. 723–730, 2012. View at Publisher · View at Google Scholar · View at Scopus
  28. N. Fujino, H. Kubo, C. Ota et al., “A novel method for isolating individual cellular components from the adult human distal lung,” The American Journal of Respiratory Cell and Molecular Biology, vol. 46, no. 4, pp. 422–430, 2012. View at Publisher · View at Google Scholar · View at Scopus
  29. M. L. Fehrenbach, G. Cao, J. T. Williams, J. M. Finklestein, and H. M. DeLisser, “Isolation of murine lung endothelial cells,” The American Journal of Physiology—Lung Cellular and Molecular Physiology, vol. 296, no. 6, pp. L1096–L1103, 2009. View at Publisher · View at Google Scholar · View at Scopus
  30. L. S. Mackay, S. Dodd, I. G. Dougall et al., “Isolation and characterisation of human pulmonary microvascular endothelial cells from patients with severe emphysema,” Respiratory Research, vol. 14, article 23, 2013. View at Publisher · View at Google Scholar · View at Scopus
  31. I. Arnaoutova, J. George, H. K. Kleinman, and G. Benton, “The endothelial cell tube formation assay on basement membrane turns 20: state of the science and the art,” Angiogenesis, vol. 12, no. 3, pp. 267–274, 2009. View at Publisher · View at Google Scholar · View at Scopus
  32. E. R. Weibel and G. E. Palade, “New cytoplasmic components in arterial endothelia,” The Journal of Cell Biology, vol. 23, pp. 101–112, 1964. View at Publisher · View at Google Scholar · View at Scopus
  33. E. Sölder, B. C. Böckle, V. A. Nguyen et al., “Isolation and characterization of CD133+ CD34+ VEGFR-2+ CD45− fetal endothelial cells from human term placenta,” Microvascular Research, vol. 84, no. 1, pp. 65–73, 2012. View at Publisher · View at Google Scholar · View at Scopus
  34. A. Woodfin, M.-B. Voisin, and S. Nourshargh, “PECAM-1: a multi-functional molecule in inflammation and vascular biology,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 27, no. 12, pp. 2514–2523, 2007. View at Publisher · View at Google Scholar · View at Scopus
  35. P. Baluk, J. Fuxe, H. Hashizume et al., “Functionally specialized junctions between endothelial cells of lymphatic vessels,” Journal of Experimental Medicine, vol. 204, no. 10, pp. 2349–2362, 2007. View at Publisher · View at Google Scholar · View at Scopus
  36. M. A. Lemmon and J. Schlessinger, “Cell signaling by receptor tyrosine kinases,” Cell, vol. 141, no. 7, pp. 1117–1134, 2010. View at Publisher · View at Google Scholar · View at Scopus
  37. K. Alitalo, T. Tammela, and T. V. Petrova, “Lymphangiogenesis in development and human disease,” Nature, vol. 438, no. 7070, pp. 946–953, 2005. View at Publisher · View at Google Scholar · View at Scopus
  38. R. S. Herbst, J. V. Heymach, and S. M. Lippman, “Molecular origins of cancer: lung cancer,” New England Journal of Medicine, vol. 359, no. 13, pp. 1367–1380, 2008. View at Publisher · View at Google Scholar · View at Scopus
  39. G. Liang, Z. Liu, J. Wu, Y. Cai, and X. Li, “Anticancer molecules targeting fibroblast growth factor receptors,” Trends in Pharmacological Sciences, vol. 33, no. 10, pp. 531–541, 2012. View at Publisher · View at Google Scholar · View at Scopus
  40. M. M. Chitnis, J. S. P. Yuen, A. S. Protheroe, M. Pollak, and V. M. Macaulay, “The type 1 insulin-like growth factor receptor pathway,” Clinical Cancer Research, vol. 14, no. 20, pp. 6364–6370, 2008. View at Publisher · View at Google Scholar · View at Scopus
  41. J. S. de Bono and T. A. Yap, “c-MET: an exciting new target for anticancer therapy,” Therapeutic Advances in Medical Oncology, vol. 3, no. 1, supplement, pp. S3–S5, 2011. View at Publisher · View at Google Scholar
  42. Y. Feng, P. S. Thiagarajan, and P. C. Ma, “MET signaling: novel targeted inhibition and its clinical development in lung cancer,” Journal of Thoracic Oncology, vol. 7, no. 2, pp. 459–467, 2012. View at Publisher · View at Google Scholar · View at Scopus
  43. R. Cao, M. A. Björndahl, P. Religa et al., “PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis,” Cancer Cell, vol. 6, no. 4, pp. 333–345, 2004. View at Publisher · View at Google Scholar · View at Scopus
  44. R. Romon, E. Adriaenssens, C. Lagadec, E. Germain, H. Hondermarck, and X. Le Bourhis, “Nerve growth factor promotes breast cancer angiogenesis by activating multiple pathways,” Molecular Cancer, vol. 9, article 157, 2010. View at Publisher · View at Google Scholar · View at Scopus
  45. K. Nakamura, F. Tan, Z. Li, and C. J. Thiele, “NGF activation of TrkA induces vascular endothelial growth factor expression via induction of hypoxia-inducible factor-1α,” Molecular and Cellular Neuroscience, vol. 46, no. 2, pp. 498–506, 2011. View at Publisher · View at Google Scholar · View at Scopus
  46. G. Graiani, C. Emanueli, E. Desortes et al., “Nerve growth factor promotes reparative angiogenesis and inhibits endothelial apoptosis in cutaneous wounds of type 1 diabetic mice,” Diabetologia, vol. 47, no. 6, pp. 1047–1054, 2004. View at Publisher · View at Google Scholar · View at Scopus
  47. A. Caporali, E. Pani, A. J. G. Horrevoets et al., “Neurotrophin p75 receptor (p75NTR) promotes endothelial cell apoptosis and inhibits angiogenesis: implications for diabetes-induced impaired neovascularization in ischemic limb muscles,” Circulation Research, vol. 103, no. 2, pp. e15–e26, 2008. View at Publisher · View at Google Scholar · View at Scopus
  48. H. K. Kleinman and G. R. Martin, “Matrigel: basement membrane matrix with biological activity,” Seminars in Cancer Biology, vol. 15, no. 5, pp. 378–386, 2005. View at Publisher · View at Google Scholar · View at Scopus
  49. W. C. Aird, “Endothelial cell heterogeneity,” Cold Spring Harbor Perspectives in Medicine, vol. 2, no. 1, Article ID a006429, 2012. View at Publisher · View at Google Scholar · View at Scopus