PMID- 9862726 OWN - NLM STAT- MEDLINE DCOM- 19990122 LR - 20220318 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 161 IP - 12 DP - 1998 Dec 15 TI - 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. PG - 6924-30 AB - 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. FAU - van den Berg, R H AU - van den Berg RH AD - Department of Nephrology, Leiden University Hospital, The Netherlands. FAU - Faber-Krol, M C AU - Faber-Krol MC FAU - Sim, R B AU - Sim RB FAU - Daha, M R AU - Daha MR LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Antibodies, Monoclonal) RN - 0 (CFH protein, human) RN - 0 (Calcium-Binding Proteins) RN - 0 (Calreticulin) RN - 0 (Chemokine CCL2) RN - 0 (Immunoglobulin Fab Fragments) RN - 0 (Immunoglobulin M) RN - 0 (Interleukin-6) RN - 0 (Interleukin-8) RN - 0 (Peptide Fragments) RN - 0 (Protein Synthesis Inhibitors) RN - 0 (RNA, Messenger) RN - 0 (Ribonucleoproteins) RN - 80295-33-6 (Complement C1q) RN - 80295-65-4 (Complement Factor H) RN - 98600C0908 (Cycloheximide) SB - IM MH - Animals MH - Antibodies, Monoclonal/pharmacology MH - Calcium-Binding Proteins/antagonists & inhibitors/immunology/physiology MH - Calreticulin MH - Cells, Cultured MH - Chemokine CCL2/*biosynthesis/genetics MH - Complement C1q/*pharmacology MH - Complement Factor H/analysis MH - Cycloheximide/pharmacology MH - Dose-Response Relationship, Immunologic MH - Endothelium, Vascular/*drug effects/metabolism MH - Enzyme-Linked Immunosorbent Assay MH - Humans MH - Immunoglobulin Fab Fragments/pharmacology MH - Immunoglobulin M/pharmacology MH - Interleukin-6/*biosynthesis/genetics MH - Interleukin-8/*biosynthesis/genetics MH - Peptide Fragments/pharmacology MH - Protein Synthesis Inhibitors/pharmacology MH - RNA, Messenger/biosynthesis/genetics MH - Rabbits MH - Ribonucleoproteins/antagonists & inhibitors/immunology/physiology MH - Stimulation, Chemical MH - Umbilical Veins EDAT- 1998/12/23 00:00 MHDA- 1998/12/23 00:01 CRDT- 1998/12/23 00:00 PHST- 1998/12/23 00:00 [pubmed] PHST- 1998/12/23 00:01 [medline] PHST- 1998/12/23 00:00 [entrez] PST - ppublish SO - J Immunol. 1998 Dec 15;161(12):6924-30.