期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 205, 期 8, 页码 1739-1746出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20071427
关键词
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资金
- Medical Research Council, UK
- Medical Research Council [G0401591, G0600698B, MC_U120074259] Funding Source: researchfish
- MRC [MC_U120074259, G0401591] Funding Source: UKRI
Thrombin, acting through a family of protease-activated receptors (PARs), is known to amplify inflammatory responses, but the in vivo importance of PARs in inflammation is not fully appreciated. In a mouse heart-to-rat transplant model, where it is possible to distinguish graft (mouse) from systemic (rat) chemokines, we show that donor PAR-1 is required to generate the local monocyte chemoattractant protein (MCP)-1 needed to recruit rat natural killer cells and macrophages into the hearts. We have confirmed the importance of this mechanism in a second model of thioglycollate-induced peritonitis and also show that PAR-1 is important for the production of MCP-3 and MCP-5. Despite the presence of multiple other mediators capable of stimulating chemokine production in these models, these data provide the first evidence that thrombin and PAR activation are required in vivo to initiate inflammatory cell recruitment.
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