The Journal of Experimental Medicine
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Published online July 7, 2008
doi:10.1084/jem.20071427
The Journal of Experimental Medicine
The Rockefeller University Press, 0022-1007 $30.00
© 2008 Chen et al.
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BRIEF DEFINITIVE REPORT

 Protease-activated receptor 1 activation is necessary for monocyte chemoattractant protein 1–dependent leukocyte recruitment in vivo

Daxin Chen1, Adam Carpenter2, Joel Abrahams1, Rachel C. Chambers3, Robert I. Lechler1, John H. McVey2, and Anthony Dorling1

1 Department of Immunology and 2 Haemostasis and Thrombosis, MRC Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, London W12 0NN, England, UK
3 Centre for Respiratory Research, University College London, Rayne Institute, London WC1E 6JJ, England, UK

CORRESPONDENCE Anthony Dorling: a.dorling{at}imperial.ac.uk

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.

R.I. Lechler's present address is Kings College London, Guys Campus, London SE1 1UL, England, UK.


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