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Titolo:
NEUTROPHIL ROLLING ALTERED BY INHIBITION OF L-SELECTIN SHEDDING IN-VITRO
Autore:
WALCHECK B; KAHN J; FISHER JM; WANG BB; FISK RS; PAYAN DG; FEEHAN C; BETAGERI R; DARLAK K; SPATOLA AF; KISHIMOTO TK;
Indirizzi:
BOEHRINGER INGELHEIM PHARMACEUT INC,DEPT IMMUNOL RIDGEFIELD CT 06877 BOEHRINGER INGELHEIM PHARMACEUT INC,DEPT IMMUNOL RIDGEFIELD CT 06877 BOEHRINGER INGELHEIM PHARMACEUT INC,DEPT INFLAMMATORY DIS RIDGEFIELD CT 06877 KHEPRI PHARMACEUT INC S SAN FRANCISCO CA 94080 UNIV LOUISVILLE,DEPT CHEM LOUISVILLE KY 40292 UNIV LOUISVILLE,DEPT BIOCHEM LOUISVILLE KY 40292
Titolo Testata:
Nature
fascicolo: 6576, volume: 380, anno: 1996,
pagine: 720 - 723
SICI:
0028-0836(1996)380:6576<720:NRABIO>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
ADHESION MOLECULE-1; CHEMOTACTIC FACTORS; ENDOTHELIAL-CELLS; PRECURSOR; INFLAMMATION; CLEAVAGE; PROTEIN; INVIVO; ALPHA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
32
Recensione:
Indirizzi per estratti:
Citazione:
B. Walcheck et al., "NEUTROPHIL ROLLING ALTERED BY INHIBITION OF L-SELECTIN SHEDDING IN-VITRO", Nature, 380(6576), 1996, pp. 720-723

Abstract

THE L-selectin adhesion molecule is involved in guiding leukocytes tosites of inflammation(1). L-selectin is cleaved by an unusual proteolytic activity at a membrane-proximal site resulting in rapid shedding from the cell surface(2-7). Although it has been demonstrated that L-selectin mediates, in part, the early event of leukocyte rolling under hydrodynamic flows(8-10), the contribution of shedding to L-selectin function has remained unknown. Here we show that hydroxamic acid-based metalloprotease inhibitors block L-selectin downregulation from the cell surface of stimulated neutrophils, without affecting Mac-1 mobilization or general neutrophil activation, and inhibit cleavage of L-selectin in a cell-free system. Unexpectedly, the hydroxamic acid-based inhibitors reduced neutrophil rolling velocity under hydrodynamic flow, resulting in increased neutrophil accumulation. These results suggest that L-selectin is cleaved in seconds-much faster than previously suspected-during the process of rolling under hydrodynamic flow, and that shedding of L-selectin may contribute significantly to the velocity of leukocyte rolling, L-selectin shedding during rolling interactions maybe physiologically important for limiting leukocyte aggregation and accumulation at sites of inflammation.

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Documento generato il 23/01/21 alle ore 02:56:51