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Agonists of proteinase‐activated receptor‐2 modulate human neutrophil cytokine secretion, expression of cell adhesion molecules, and migration within 3‐D collagen lattices
Author(s) -
Shpacovitch V. M.,
Varga G.,
Strey A.,
Gunzer M.,
Mooren F.,
Buddenkotte J.,
Vergnolle N.,
Sommerhoff C. P.,
Grabbe S.,
Gerke V.,
Homey B.,
Hollenberg M.,
Luger T. A.,
Steinhoff M.
Publication year - 2004
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0503221
Subject(s) - biology , microbiology and biotechnology , protease activated receptor , protease activated receptor 2 , secretion , proteases , receptor , inflammation , chemotaxis , integrin , immunology , biochemistry , enzyme linked receptor , thrombin , platelet , enzyme
Proteinase‐activated receptor‐2 (PAR 2 ) belongs to a novel subfamily of G‐protein‐coupled receptors with seven‐transmembrane domains. PAR 2 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 PAR 2 . However, the precise physiological role of PAR 2 on human neutrophils and its implication in human diseases remain unclear. We demonstrate that PAR 2 agonist‐stimulated human neutrophils show significantly enhanced migration in 3‐D collagen lattices. PAR 2 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, PAR 2 stimulation results in an increased secretion of the cytokines interleukin (IL)‐1β, IL‐8, and IL‐6 by human neutrophils. These data indicate that PAR 2 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, PAR 2 may represent a potential therapeutic target for the treatment of diseases involving activated neutrophils.