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Titolo:
Selectivity of recombinant human leukotriene D-4, leukotriene B-4, and lipoxin A(4) receptors with aspirin-triggered 15-epi-LXA(4) and regulation of vascular and inflammatory responses
Autore:
Gronert, K; Martinsson-Niskanen, T; Ravasi, S; Chiang, N; Serhan, CN;
Indirizzi:
Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury, Dept Anesthesia Perioperat & Pain Med, Boston, MA 02115 USA Brigham & Womens Hosp Boston MA USA 02115 Pain Med, Boston, MA 02115 USA Harvard Univ, Sch Med, Boston, MA USA Harvard Univ Boston MA USAHarvard Univ, Sch Med, Boston, MA USA
Titolo Testata:
AMERICAN JOURNAL OF PATHOLOGY
fascicolo: 1, volume: 158, anno: 2001,
pagine: 3 - 9
SICI:
0002-9440(200101)158:1<3:SORHLD>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
ENDOTHELIAL-CELLS; STABLE ANALOGS; P-SELECTIN; IDENTIFICATION; NEUTROPHILS; EXPRESSION; PATHWAY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
28
Recensione:
Indirizzi per estratti:
Indirizzo: Serhan, CN Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury, Dept Anesthesia Perioperat & Pain Med, 75 Francis St, Boston, MA 02115 USA Brigham & Womens Hosp 75 Francis St Boston MA USA 02115 115 USA
Citazione:
K. Gronert et al., "Selectivity of recombinant human leukotriene D-4, leukotriene B-4, and lipoxin A(4) receptors with aspirin-triggered 15-epi-LXA(4) and regulation of vascular and inflammatory responses", AM J PATH, 158(1), 2001, pp. 3-9

Abstract

Aspirin-triggered Lipoxin A(4) (ATL, 15-epi-LXA(4)) and leukotriene D-4 (LTD4) possess opposing vascular actions mediated via receptors distinct fromthe LXA(4) receptor (ALX) that is involved in leukocyte trafficking. Here,we identified these receptors by nucleotide sequencing and demonstrate that LTD4 receptor (CysLT(1)) is induced in human vascular endothelia by interkukin-1 beta. Recombinant CysLT(1) receptor gave stereospecific binding with both [H-3]-LTD4 and a novel labeled mimetic of ATL ([H-3]-ATLa) that was displaced with LTD4 and ATLa (similar to IC50 0.2 to 0.9 nmol/ L), but not with a bioinactive ATL isomer. The clinically used CysLT(1) receptor antagonist, Singulair, showed a lower rank order for competition with [H-3]-ATLa (IC50 approximate to 8.3 nmol/L). In contrast, LTD4 was an ineffective competitive ligand for recombinant ALX receptor with [H-3]-ATLa, and ATLa did not compete for [H-3]-LTB4 binding with recombinant LTB4 receptor. Endogenous murine CysLT(1) receptors also gave specific [H-3]-ATLa binding that was displaced with essentially equal affinity by LTD, or ATLa, Systemic ATLa proved to be a potent inhibitor (>50%) of CysLT(1)-mediated vascular leakage in murine skin (200 mug/kg) in addition to its ability to block polymorphonuclear leukocyte recruitment to dorsal air pouch (4 mug/kg). These results indicate that ATL and LTD, bind and compete with equal affinity at CysLT(1), providing a molecular basis for aspirin-triggered LXs serving as a local damper of both vascular CysLT(1) signals as well as ALX receptor-regulated polymorphonuclear leukocyte traffic.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/04/20 alle ore 10:54:53