Ecotin-Like ISP of L. major Promastigotes Fine-Tunes Macrophage Phagocytosis by Limiting the Pericellular Release of Bradykinin from Surface-Bound Kininogens: A Survival Strategy Based on the Silencing of Proinflammatory G-Protein Coupled Kinin B2 and B1 Receptors
Figure 5
Scheme shows how ISP-2 limits the kinin-releasing activity of surface S1A-proteases of macrophages. As an extension of recently published studies [27, 31, 32], here we propose that the proinflammatory phenotype of the mutant (right side of scheme) is due to increased pericellular release of kinins mediated by NE and/or contact phase serine proteases (FXIIa/PKa). In the absence of ISP-2, the “eat me signal” of kininogen tethered on L. major mutants might be inactivated by S1A-family proteases. In addition, the released kinin peptides fuel phagocytosis and microbicidal function of macrophages via activation of B2R and B1R, a subtype of GPCR upregulated in inflamed tissues.
