Journal of Leukocyte Biology
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Originally published online as doi:10.1189/jlb.0704422 on July 6, 2005

Published online before print July 6, 2005
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(Journal of Leukocyte Biology. 2005;78:967-975.)
© 2005 by Society for Leukocyte Biology

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

Ulrika Johansson*, Charlotte Lawson{dagger}, Michael Dabare{ddagger}, Denise Syndercombe-Court*, Adrian C. Newland*, Gareth L. Howells{ddagger} and Marion G. Macey*,1

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

1Correspondence: Barts and The Royal London Hospital Medical School Haematology, Whitechapel, London, E1 1BB, UK. E-mail: marion.macey{at}bartsandthelondon.nhs.uk

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)-1ß, 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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