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Indomethacin Causes Prostaglandin D2-like and Eotaxin-like Selective Responses in Eosinophils and Basophils

2002; Elsevier BV; Volume: 277; Issue: 29 Linguagem: Inglês

10.1074/jbc.m201803200

1083-351X

Victoria Stubbs, Petra Schratl, Adele Hartnell, Timothy J. Williams, Bernhard A. Peskar, Ákos Heinemann, Ian Sabroe,

Urticaria and Related Conditions

We investigated the actions of a panel of nonsteroidal anti-inflammatory drugs on eosinophils, basophils, neutrophils, and monocytes. Indomethacin alone was a potent and selective inducer of eosinophil and basophil shape change. In eosinophils, indomethacin induced chemotaxis, CD11b up-regulation, respiratory burst, and L-selectin shedding but did not cause up-regulation of CD63 expression. Pretreatment of eosinophils with indomethacin also enhanced subsequent eosinophil shape change induced by eotaxin, although treatment with higher concentrations of indomethacin resulted in a decrease in the expression of the major eosinophil chemokine receptor, CCR3. Indomethacin activities and cell selectivity closely resembled those of prostaglandin D 2 (PGD 2 ). Eosinophil shape change in response to eotaxin was inhibited by pertussis toxin, but indomethacin- and PGD 2 -induced shape change responses were not. Treatment of eosinophils with specific inhibitors of phospholipase C (U-73122), phosphatidylinositol 3-kinase (LY-294002), and p38 mitogen-activated protein kinase (SB-202190) revealed roles for these pathways in indomethacin signaling. Indomethacin and its analogues may therefore provide a structural basis from which selective PGD 2 receptor small molecule antagonists may be designed and which may have utility in the treatment of allergic inflammatory disease.