The first subcomponent of complement, C1q, triggers the production of IL-8, IL-6, and monocyte chemoattractant peptide-1 by human umbilical vein endothelial cells

We and others have demonstrated previously the occurrence of cC1qR/CaR, a r eceptor For the collagen-like stalks of complement component C1q, on endoth elial cells. In the present study we investigated whether binding of C1q to endothelial cells resulted in enhancement of cytokine of chemokine product ion. HUVEC produced 82 +/- 91 pg/ml of IL-8, 79 +/- 113 pg/ml of lL-6, and 503 +/- 221 pg/ml of monocyte chemoattractant peptide-1 (MCP-1) under basal conditions, Incubation with C1q resulted in a time- and dose-dependent up- regulation of IL-8 (1012 +/- 43 pg/ml), IL-6 (392 +/- 20 pg/ml), and MCP-1 (2450 +/- 101 pg/ml), This production is dependent on de nova protein synth esis, as demonstrated by the detection of specific mRNA after C1q stimulati on, and inhibition of peptide production in the presence of cycloheximide, The production of all factors was inhibited (69 +/- 7%) by the collagenous fragments of C1q, while the C1q globular heads only induced 13 +/- 11% inhi bition. When HUVEC were incubated with C1q in the presence of aggregated Ig M, enhanced production of IL-8 (2500 +/- 422 pg/ml), IL-6 (997 +/- 21 pg/ml ), and MCP-1 (5343 +/- 302 pg/ml) was found. Furthermore, F(ab')(2) anti-ca lreticulin partially inhibited the production of IL-8, confirming at least the involvement of cC1qR/CaR, These experiments suggest that in an inflamma tory response C1q not only is able to activate the complement pathway, but when presented, in a proper fashion also might induce the production of fac tors that contribute to acute phase responses and recruitment of inflammato ry cells.