Posttranslational Modifications Affect the Activity of the Human Monocyte Chemotactic Proteins MCP-1 and MCP-2: Identification of MCP-2(6–76) as a Natural Chemokine Inhibitor

作者：Paul Proost, Sofie Struyf, Mikaël Couvreur, Jean‐Pierre Lenaerts, René Conings, Patricia Menten, Peter D. E. M. Verhaert, Anja Wuyts, Jo Van Damme · 发表于：The Journal of Immunology · 年份：1998 · DOI：10.4049/jimmunol.160.8.4034 · 被引用次数：129 · 研究领域：Chemokine receptors and signaling、Immunotherapy and Immune Responses、T-cell and B-cell Immunology

Chemokines are important mediators in infection and inflammation. The monocyte chemotactic proteins (MCPs) form a subclass of structurally related C-C chemokines. MCPs select specific target cells due to binding to a distinct set of chemokine receptors. Recombinant and synthetic MCP-1 variants have been shown to function as chemokine antagonists. In this study, posttranslationally modified immunoreactive MCP-1 and MCP-2 were isolated from mononuclear cells. Natural forms of MCP-1 and MCP-2 were biochemically identified by Edman degradation and mass spectrometry and functionally characterized in chemotaxis and Ca2+-mobilization assays. Glycosylated MCP-1 (12 and 13.5 kDa) was found to be two- to threefold less chemotactic for monocytes and THP-1 cells than nonglycosylated MCP-1 (10 kDa). Natural, NH2-terminally truncated MCP-1(5-76) and MCP-1(6-76) were practically devoid of bioactivity, whereas COOH-terminally processed MCP-1(1-69) fully retained its chemotactic and Ca2+-inducing capacity. The capability of naturally modified MCP-1 forms to desensitize the Ca2+ response induced by intact MCP-1 in THP-1 cells correlated with their agonistic potency. In contrast, naturally modified MCP-2(6-76) was devoid of activity, but could completely block the chemotactic effect of intact MCP-2 as well as that of MCP-1, MCP-3, and RANTES. Carboxyl-terminally processed MCP-2(1-74) did retain its chemotactic potency. Although comparable as a chemoattractant, natural intact MCP-2 was found to ...