The seventh complement component is expressed on endothelial cells membrane and exerts an anti-inflammatory action

C7 is essential for the assembly of the terminal C complex (TCC) that elicits inflammatory effects on endothelial cells (ECs) both as a sublytic and cytolytically inactive complex (sC5b-9). We have previously showed that cultured HUVECs express a membrane form of C7 (mC7) which interacts with the other late C components to form membrane-bound TCC (mTCC). Soluble C7 secreted by ECs and mC7 are differently modulated by cytokines. More recently, we found that mC7 can be detected on the microvascular endothelium of frozen sections of human decidua and skin and on ECs isolated from these tissues. Sequence analysis of affinity-purified mC7 revealed that mC7 is identical to the soluble molecule. In addition, we found that mC7 is linked to vimentin as revealed by co-immune precipitation and co-localization on the cell surface. Since we previously observed that mTCC, unlike sC5b-9, does not induce pro-inflammatory effects on ECs, we decided to ascertain whether the assembly of mTCC on ECs would make these cells refractory to the stimulating effect of sC5b-9 providing a negative signal to the ECs. This was assessed by first incubating C7-bearing ECs with C5b6, C8 and C9 for 1 h and then exposing the cells to sC5b-9. Under these conditions, we failed to observe expression of adhesion molecules, secretion of IL-8 and increase of albumin leakage normally induced by sC5b-9 on ECs bearing only mC7. In conclusions, we have shown that ECs express mC7 linked to vimentin and structurally similar to secreted C7. This membrane-bound molecule maintains the ability to form TCC, which fails to induce pro-inflammatory effects on ECs, and down-modulates the stimulating