Human peripheral blood monocytes express protease receptor-2 and respond to receptor activation by production of IL-6, IL-8, and IL-1{beta}.
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)-1beta, 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.
Johansson
Ulrika
U
Department of Haematology, Barts and the London NHS Trust, London, E1 1BB, UK.
Lawson
Charlotte
C
Dabare
Michael
M
Syndercombe-Court
Denise
D
Newland
Adrian C
AC
Howells
Gareth L
GL
Macey
Marion G
MG
D002118:Calcium / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000276:immunology; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D009000:Monocytes / Q000276:immunology*; D044464:Receptor, PAR-2 / Q000096:biosynthesis* / Q000276:immunology*
D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D044464:Receptor, PAR-2; D002118:Calcium