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 receptor for the collagen-like stalks of complement component C1q, on endothelial cells. In the present study we investigated whether binding of C1q to endothelial cells resulted in enhancement of cytokine or chemokine production. HUVEC produced 82 +/- 91 pg/ml of IL-8, 79 +/- 113 pg/ml of IL-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 novo protein synthesis, as demonstrated by the detection of specific mRNA after C1q stimulation, 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% inhibition. When HUVEC were incubated with C1q in the presence of aggregated IgM, 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-calreticulin partially inhibited the production of IL-8, confirming at least the involvement of cC1qR/CaR. These experiments suggest that in an inflammatory response C1q not only is able to activate the complement pathway, but when presented in a proper fashion also might induce the production of factors that contribute to acute phase responses and recruitment of inflammatory cells.
van den Berg
R H
RH
Department of Nephrology, Leiden University Hospital, The Netherlands.
Faber-Krol
M C
MC
Sim
R B
RB
Daha
M R
MR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology; D037282:Calreticulin; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics; D015922:Complement C1q / Q000494:pharmacology*; D017242:Complement Factor H / Q000032:analysis; D003513:Cycloheximide / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D007075:Immunoglobulin M / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D010446:Peptide Fragments / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011817:Rabbits; D012261:Ribonucleoproteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology; D013268:Stimulation, Chemical; D014471:Umbilical Veins
D000911:Antibodies, Monoclonal; C493495:CFH protein, human; D002135:Calcium-Binding Proteins; D037282:Calreticulin; D018932:Chemokine CCL2; D007140:Immunoglobulin Fab Fragments; D007075:Immunoglobulin M; D015850:Interleukin-6; D016209:Interleukin-8; D010446:Peptide Fragments; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D012261:Ribonucleoproteins; D015922:Complement C1q; D017242:Complement Factor H; D003513:Cycloheximide