Endothelial serpins--protectors of the vasculature?
Vascular damage, initiated by host inflammatory cells, is a component of the pathophysiology of many acute and chronic inflammatory disorders. Neutrophil-mediated tissue damage is mediated primarily by proteinases, particularly elastase and cathepsin G. In this study we have identified endothelial binding of two key serine proteinase inhibitors (serpins), alpha 1-antitrypsin, the inhibitor of elastase, and alpha 1-antichymotrypsin, the inhibitor of cathepsin G. These serpins are shed from the endothelium into the supernatant when neutrophils adherent to the endothelium are activated. Endothelium activated by lipopolysaccharide (LPS) augments this process. Serpin-proteinase complexes activate neutrophils and induce further cytokine release, thereby amplifying inflammatory processes. Strategies aimed at preventing endothelial serpin depletion may help minimize vascular damage during inflammation.
Forsyth
K D
KD
Department of Paediatrics and Child Health, Flinders Medical Centre, Adelaide, S. Australia.
Talbot
V
V
Beckman
I
I
D000328:Adult; D056649:Cathepsin G; D002403:Cathepsins / Q000032:analysis; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000737:chemistry* / Q000502:physiology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology; D012697:Serine Endopeptidases; D015843:Serpins / Q000032:analysis* / Q000502:physiology; D000514:alpha 1-Antichymotrypsin / Q000032:analysis; D000515:alpha 1-Antitrypsin / Q000032:analysis
D008070:Lipopolysaccharides; D015843:Serpins; D000514:alpha 1-Antichymotrypsin; D000515:alpha 1-Antitrypsin; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G