C7 is expressed on endothelial cells as a trap for the assembling terminal complement complex and may exert anti-inflammatory function.
We describe a novel localization of C7 as a membrane-bound molecule on endothelial cells (ECs). Data obtained by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), Western blot analysis, Northern blot analysis, and mass spectrometry revealed that membrane-associated C7 (mC7) was indistinguishable from soluble C7 and was associated with vimentin on the cell surface. mC7 interacted with the other late complement components to form membrane-bound TCC (mTCC). Unlike the soluble SC5b-9, mTCC failed to stimulate ECs to express adhesion molecules, to secrete IL-8, and to induce albumin leakage through a monolayer of ECs, and more importantly protected ECs from the proinflammatory effect of SC5b-9. Our data disclose the possibility of a novel role of mC7 that acts as a trap for the late complement components to control excessive inflammation induced by SC5b-9.
Bossi
Fleur
F
Department of Life Sciences, University of Trieste, Trieste, Italy.
Rizzi
Lucia
L
Bulla
Roberta
R
Debeus
Alessandra
A
Tripodo
Claudio
C
Picotti
Paola
P
Betto
Elena
E
Macor
Paolo
P
Pucillo
Carlo
C
Würzner
Reinhard
R
Tedesco
Francesco
F
D002478:Cells, Cultured; D003184:Complement C7 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D015938:Complement Membrane Attack Complex / Q000276:immunology / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism; D040901:Proteomics; D012333:RNA, Messenger / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology; D014657:Vasculitis / Q000276:immunology* / Q000378:metabolism*; D014746:Vimentin / Q000378:metabolism
D003184:Complement C7; D015938:Complement Membrane Attack Complex; D016209:Interleukin-8; D008565:Membrane Proteins; D012333:RNA, Messenger; D014746:Vimentin