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原文链接如下:希望大家以后提供各类重要信息的时候,最好能注明出处
1 `2 T t( f7 x+ jGastrin-releasing peptide receptor (GRPR) mediates chemotaxis in neutrophils
3 I/ S9 S( N; q5 b a! h5 M, iNeutrophil migration to inflamed sites is crucial for both the initiation of inflammation and resolution of infection, yet these cells are involved in perpetuation of different chronic inflammatory diseases. Gastrin-releasing peptide (GRP) is a neuropeptide that acts through G protein coupled receptors (GPCRs) involved in signal transmission in both central and peripheral nervous systems. Its receptor, gastrin-releasing peptide receptor (GRPR), is expressed by various cell types, and it is overexpressed in cancer cells. RC-3095 is a selective GRPR antagonist, recently found to have antiinflammatory properties in arthritis and sepsis models. Here we demonstrate that i.p. injection of GRP attracts neutrophils in 4 h, and attraction is blocked by RC-3095. Macrophage depletion or neutralization of TNF abrogates GRP-induced neutrophil recruitment to the peritoneum. In vitro, GRP-induced neutrophil migration was dependent on PLC-β2, PI3K, ERK, p38 and independent of Gαi protein, and neutrophil migration toward synovial fluid of arthritis patients was inhibited by treatment with RC-3095. We propose that GRPR is an alternative chemotactic receptor that may play a role in the pathogenesis of inflammatory disorders.
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) Z- Y2 ?& o# `2 ?# ?3 G作 者:Czepielewski, Rafael Sanguinetti; Porto, Bárbara Nery; Rizzo, Lucas Bortolotto; Roesler, Rafael; Abujamra, Ana Lúcia; Pinto, Larissa Garcia; Schwartsmann, Gilberto; Cunha, Fernando de Queiroz; Bonorino, Cristina
% v- C, P! w) W; U期刊名称: Proceedings of the National Academy of Sciences
# g) [4 z; }/ }7 }9 F+ ~, E期卷页: 01/10/2012 第109卷 第2期 547~552页 ( \5 Y/ f9 e5 M; F; c: N* z
原文链接:http://www.pnas.org/content/109/ ... 9-85e7-8d1b770e90ff 3 M9 \8 `( P+ v3 m0 |8 D+ S$ g
DOI: 10.1073/pnas.1110996109 : g# k; t z& `3 C
ISBN: 0027-8424
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