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PMID:15155775

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Citation

Shpacovitch, VM, Varga, G, Strey, A, Gunzer, M, Mooren, F, Buddenkotte, J, Vergnolle, N, Sommerhoff, CP, Grabbe, S, Gerke, V, Homey, B, Hollenberg, M, Luger, TA and Steinhoff, M (2004) Agonists of proteinase-activated receptor-2 modulate human neutrophil cytokine secretion, expression of cell adhesion molecules, and migration within 3-D collagen lattices. J. Leukoc. Biol. 76:388-98

Abstract

Proteinase-activated receptor-2 (PAR2) belongs to a novel subfamily of G-protein-coupled receptors with seven-transmembrane domains. PAR2 can be activated by serine proteases such as trypsin, mast cell tryptase, and allergic or bacterial proteases. This receptor is expressed by various cells and seems to be crucially involved during inflammation and the immune response. As previously reported, human neutrophils express functional PAR2. However, the precise physiological role of PAR2 on human neutrophils and its implication in human diseases remain unclear. We demonstrate that PAR2 agonist-stimulated human neutrophils show significantly enhanced migration in 3-D collagen lattices. PAR2 agonist stimulation also induced down-regulation of L-selectin display and up-regulation of membrane-activated complex-1 very late antigen-4 integrin expression on the neutrophil cell surface. Moreover, PAR2 stimulation results in an increased secretion of the cytokines interleukin (IL)-1beta, IL-8, and IL-6 by human neutrophils. These data indicate that PAR2 plays an important role in human neutrophil activation and may affect key neutrophil functions by regulating cell motility in the extracellular matrix, selectin shedding, and up-regulation of integrin expression and by stimulating the secretion of inflammatory mediators. Thus, PAR2 may represent a potential therapeutic target for the treatment of diseases involving activated neutrophils.

Links

PubMed Online version:10.1189/jlb.0503221

Keywords

Calcium/metabolism; Cell Adhesion Molecules/biosynthesis; Cell Adhesion Molecules/genetics; Cytokines/metabolism; Female; Humans; Interleukins/metabolism; L-Selectin/metabolism; Male; Neutrophils/metabolism; Receptors, Proteinase-Activated/agonists; Up-Regulation

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:PAR2

involved_in

GO:0032757: positive regulation of interleukin-8 production

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PAR2

involved_in

GO:0032755: positive regulation of interleukin-6 production

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PAR2

involved_in

GO:0032731: positive regulation of interleukin-1 beta production

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PAR2

involved_in

GO:0042119: neutrophil activation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PAR2

involved_in

GO:0050900: leukocyte migration

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PAR2

involved_in

GO:0050702: interleukin-1 beta secretion

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PAR2

involved_in

GO:2000484: positive regulation of interleukin-8 secretion

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PAR2

involved_in

GO:2000778: positive regulation of interleukin-6 secretion

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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