Cooperation of C1q receptors and integrins in C1q-mediated endothelial cell adhesion and spreading

Xiaodong Feng, Marcia G. Tonnesen, Ellinor I.B. Peerschke, Berhane Ghebrehiwet

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

Abstract

The interaction of C1q with endothelial cells elicits a multiplicity of biologic responses. Although these responses are presumed to be mediated by the interaction of C1q with endothelial cell surface proteins, the identity of the participants is not known. In this study we examined the roles of two C1q binding proteins, cC1q-R/calreticulin and gC1q-R/p33, in C1q-mediated adhesion and spreading of human dermal microvascular endothelial cells (HDMVEC). When HDMVEC were cultured in microtiter plate wells coated with concentrations of C1q ranging from 0 to 50 μg/ml, a specific and dose-dependent adhesion and spreading was observed. The extent of adhesion and spreading was similar to the adhesion seen on collagen-coated wells. Spreading (68 ± 12%) and to a moderate extent adhesion (47 ± 9%) were inhibited by anti-gC1q-R mAb 60.11. Similar effects were noted with polyclonal anti-cC1q-R but not with control nonimmune IgG. The two Abs had a slight additive effect (75 ± 13% inhibition) when mixed together in the proportion of 100/μg/ml anti-gC1q-R and 30 μg/ml anti-cC1q-R. More importantly, a 100% inhibition of spreading, but not adhesion, to C1q-coated wells was observed when HDMVEC were cultured in the presence of 30/μM of the peptide GRRGDSP but not GRRGESP. Furthermore, while anti-β1 integrin Ab blocked both adhesion and spreading, anti-α5 integrin blocked only spreading and not adhesion. Ag capture ELISA of endothelial cell membrane proteins using polyclonal anti-gC1q-R showed the presence of not only β1 and α5 integrins but also CD44. Taken together these results suggest that endothelial cell adhesion and spreading require the cooperation of both C1qRs and β1 integrins and possibly other membrane-spanning molecules.

Original languageEnglish
Pages (from-to)2441-2448
Number of pages8
JournalJournal of Immunology
Volume168
Issue number5
DOIs
StatePublished - 1 Mar 2002
Externally publishedYes

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