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Titolo:
Matrix metalloproteinases regulate neutrophil-endothelial cell adhesion through generation of endothelin-1[1-32]
Autore:
Fernandez-Patron, C; Zouki, C; Whittal, R; Chan, JSD; Davidge, ST; Filep, JG;
Indirizzi:
Univ Montreal, Maisonneuve Rosemont Hosp, Res Ctr, Montreal, PQ H1T 2M4, Canada Univ Montreal Montreal PQ Canada H1T 2M4 tr, Montreal, PQ H1T 2M4, Canada Univ Montreal, Dept Med, Montreal, PQ H1T 2M4, Canada Univ Montreal Montreal PQ Canada H1T 2M4 ed, Montreal, PQ H1T 2M4, Canada Univ Alberta, Perinatal Res Ctr, Edmonton, AB T6G 2S2, Canada Univ Alberta Edmonton AB Canada T6G 2S2 Ctr, Edmonton, AB T6G 2S2, Canada Univ Alberta, Dept Chem, Lab Mass Spectrometry, Edmonton, AB T6G 2S2, Canada Univ Alberta Edmonton AB Canada T6G 2S2 try, Edmonton, AB T6G 2S2, Canada
Titolo Testata:
FASEB JOURNAL
fascicolo: 12, volume: 15, anno: 2001,
pagine: 2230 - 2240
SICI:
0892-6638(200110)15:12<2230:MMRNCA>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACTIVATED PROTEIN-KINASE; HUMAN POLYMORPHONUCLEAR LEUKOCYTES; METHIONYL-LEUCYL-PHENYLALANINE; C-REACTIVE PROTEIN; BIG ENDOTHELIN-1; L-SELECTIN; RECEPTOR SUBTYPE; NITRIC-OXIDE; MAP KINASE; IN-VITRO;
Keywords:
gelatinases; ETA receptor; L-selectin; CD11b/CD18; leukocyte trafficking; endothelium; inflammation;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
51
Recensione:
Indirizzi per estratti:
Indirizzo: Filep, JG Univ Montreal, Maisonneuve Rosemont Hosp, Res Ctr, 5415 Blvd Assompt, Montreal, PQ H1T 2M4, Canada Univ Montreal 5415 Blvd Assompt MontrealPQ Canada H1T 2M4 anada
Citazione:
C. Fernandez-Patron et al., "Matrix metalloproteinases regulate neutrophil-endothelial cell adhesion through generation of endothelin-1[1-32]", FASEB J, 15(12), 2001, pp. 2230-2240

Abstract

We recently reported that matrix metalloproteinase 2 (MMP-2, gelatinase A)cleaves big endothelin 1 (ET-1), yielding the vasoactive peptide ET-1[1-32]. We tested whether ET-1[1-32] could affect the adhesion of human neutrophils to coronary artery endothelial cells (HCAEC). ET-1[1-32] rapidly downregulated the expression of L-selectin and up-regulated expression of CD11b/CD18 on the neutrophil surface, with EC50 values of 1-3 nM. These actions ofET-1[1-32] were mediated via ETA receptors and did not require conversion of ET-1[1-32] into ET-1 by neutrophil proteases, as revealed by liquid chromatography and mass spectroscopy. Moreover, ET-1[1-32] evoked release of neutrophil gelatinase B, which cleaved big ET-1 to yield ET-1[1-32], thus revealing a positive feedback loop for ET-1[1-32] generation. Up-regulation ofCD11b/CD18 expression and gelatinase release was tightly associated with activation of extracellular signal-regulated kinase (Erk). Stimulation of Erk activity was due to activation of Ras, Raf-1, and MEK (MAPK kinase). ET-1[1-32] also produced slight increases in the expression of ICAM-1 and E-selectin on HCAEC, and markedly enhanced beta (2) integrin-dependent adhesion of neutrophils to activated HCAEC. These results are the first indication that gelatinolytic MMPs via cleavage of big ET-1 to yield ET-1[1-32] activate neutrophils and promote leukocyte-endothelial cell adhesion and, consequently, neutrophil trafficking into inflamed tissues.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/07/20 alle ore 01:42:01