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Gastrin-releasing peptide receptor (GRPR) mediates chemotaxis in neutrophils

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Gastrin-releasing peptide receptor (GRPR) mediates chemotaxis in neutrophils

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Título Gastrin-releasing peptide receptor (GRPR) mediates chemotaxis in neutrophils
Autor 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 Beatriz Cazabuena
Abstract Neutrophil 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.
Contido em Proceedings of the National Academy of Sciences of the United States of America. Washington. Vol. 109, no. 2 (Jan. 2012), p. 547–552
Assunto Neutrófilos
Receptores da bombesina
Origem Estrangeiro
Tipo Artigo de periódico
URI http://hdl.handle.net/10183/132070
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