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Published online before print July 6, 2005

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0704422

Received for publication September 28, 2004.
Revised April 25, 2005.
Accepted for publication May 9, 2005.

Article

Human peripheral blood monocytes express protease receptor-2 and respond to receptor activation by production of IL-6, IL-8, and IL-1

Ulrika Johansson ^*, Charlotte Lawson , Michael Dabare , Denise Syndercombe-Court ^*, Adrian C. Newland ^*, Gareth L. Howells , and Marion G. Macey ^*@

*Department of Haematology, Barts and The London NHS Trust, United Kingdom; Royal Veterinary College Royal College Street, London, United Kingdom; and Diagnostic Oral Sciences, Clinical Sciences Research Centre, Queen Mary’s School of Medicine and Dentistry, London, United Kingdom

^@ To whom correspondence should be addressed. E-mail: marion.macey{at}bartsandthelondon.nhs.uk.

	Abstract

Protease-activated receptor-2 (PAR-2) belongs to a family of G-coupled receptors activated by proteolytic cleavage to reveal a tethered ligand. PAR-2 is activated by trypsin and trypsin-like serine proteases and experimentally, by receptor-activating peptides (APs), which mimic the tethered ligand. PAR-2 has recently been implicated in proinflammatory immune responses. For example, PAR-2^-/- mice exhibit markedly diminished contact hypersensitivity reactions and are completely resistant to adjuvant-induced arthritis. The present study shows that human blood monocytes express low-level cell-surface PAR-2 ex vivo, which is up-regulated upon cell purification by the mobilization of intracellular stores of PAR-2 protein. PAR-2 expression is also present on monocyte-derived macrophages, but only a small proportion of monocyte-derived dendritic cells (DC) is PAR-2⁺, and blood DC are PAR^-. Freshly isolated monocytes responded to the PAR-2 AP ASKH 95 (2-furoyl-LIGKV-OH) with the generation of a calcium flux and production of interleukin (IL)-1, IL-6, and IL-8. The results presented thus suggest that PAR-2 contributes to inflammatory responses by inducing the production of proinflammatory cytokines in peripheral blood monocytes.

Key Words: protease-activated receptors • flow cytometry • cytokines • PAR-2

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