Inhibition of neutrophil-endothelial cell adhension by a neutrophil product, cathepsin G.
In the present study we investigated the modulation of the polymorphonuclear neutrophil (PMN)-endothelial cell adhesion process by the two main proteinases released from activated PMN during their adhesion to endothelium. Our results showed that, in contrast with elastase, cathepsin G was a powerful inhibitor of PAIN adhesion to interleukin-1 (IL-1)-treated human umbilical vein endothelial cells. This inhibitory effect was linked to the enzymatic activity of the proteinase and was selectively directed against PMN. Because the viability and the reactivity of PMN were not modified by cathepsin G, we looked for a possible effect on adhesion molecules. L-selectin was not cleaved by cathepsin G, whereas it was by chymotrypsin, a closely related proteinase. Cathepsin G blocked PMN adhesion to activated endothelial cells, but also to serum- or fibrinogen-coated plates, three adhesion processes mediated by CD11b/CD18. However, by FACScan analysis or by immunoprecipitation, we failed to find evidence of modifications of CD11b/CD18 expression. Although the precise molecular target(s) of cathepsin G remain(s) to be defined, these data indicate that this proteinase, which is known as an inflammatory mediator, can also be considered as a potential down-regulator of adhesion reactions involved in the inflammatory process.
Renesto
P
P
Unité de Pharamacologie Cellulaire, Unité Associée IP/INSERM 285, Institut Pasteur, Paris, France.
Halbwachs-Mecarelli
L
L
Bessou
G
G
Balloy
V
V
Chignard
M
M
D018821:CD18 Antigens / Q000032:analysis; D056649:Cathepsin G; D002403:Cathepsins / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D019041:L-Selectin / Q000032:analysis; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000494:pharmacology*
D018821:CD18 Antigens; D007375:Interleukin-1; D019041:L-Selectin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G