| First Author | Czepielewski RS | Year | 2012 |
| Journal | Proc Natl Acad Sci U S A | Volume | 109 |
| Issue | 2 | Pages | 547-52 |
| PubMed ID | 22203955 | Mgi Jnum | J:179982 |
| Mgi Id | MGI:5304960 | Doi | 10.1073/pnas.1110996109 |
| Citation | Czepielewski RS, et al. (2012) Gastrin-releasing peptide receptor (GRPR) mediates chemotaxis in neutrophils. Proc Natl Acad Sci U S A 109(2):547-52 |
| abstractText | 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-beta2, PI3K, ERK, p38 and independent of Galphai 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. |
