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INFLAMMATION AND IMMUNOPHARMACOLOGY

Effects of Prostaglandin D₂ and 5-Lipoxygenase Products on the Expression of CD203c and CD11b by Basophils

Immunology Laboratory, Lyon-Sud University Hospital, Pierre-Bénite Lyon, France (G.M., R.B., J.B.); Meakins-Christie Laboratories, Department of Medicine, McGill University, Montreal, Quebec, Canada (S.G., C.C., W.S.P.); and Claude Pepper Institute and Department of Chemistry, Florida Institute of Technology, Melbourne, Florida (J.R.)

Basophils are important in allergic diseases such as asthma because they produce a variety of inflammatory mediators. Activation of these cells with IgE and N-formyl-methionyl-leucyl-phenylalanine results in a variety of responses, including increased surface expression of CD203c and CD11b and release of histamine. Although considerable information is available on the effects of eicosanoids on neutrophils, eosinophils, and monocytes, less is known about their effects on basophils. In the present study, we examined the effects of various eicosanoids on the above basophil responses. Of the naturally occurring eicosanoids tested, prostaglandin D₂ (PGD₂; EC₅₀, 10 nM) was by far the most potent activator of CD203c expression, with other prostanoids having little effect. This response was mediated by the DP₂ receptor/chemoattractant receptor-homologous molecule expressed on Th2 cells because it was shared by the selective agonist 15R-methyl-PGD₂ (EC₅₀, 3 nM). The 5-lipoxygenase products leuko-triene B₄ and 5-oxo-6,8,11,14-eicosatetraenoic acid also stimulated CD203c expression but to a lesser extent than PGD₂, whereas leukotriene D₄ was inactive. Neither PGD₂ nor 5-oxo-6,8,11,14-eicosatetraenoic acid stimulated histamine release or CD63 expression on basophils. Both PGE₂ and the DP₁ receptor agonist BW245C [(4S)-(3-[(3R,S)-3-cyclohexyl-3-hydroxypropyl]-2,5-dioxo)-4-imidazolidineheptanoic acid] strongly inhibited DP₂ receptor-mediated CD203c expression. The DP₁ receptor antagonist BWA868C [3-[(2-cyclohexyl-2-hydroxyethyl)amino]-2,5-dioxo-1-(phenylmethyl)-4-imidazolidine-heptanoic acid] enhanced PGD₂-induced CD203c expression, suggesting that interaction of PGD₂ with DP₁ receptors can limit activation of basophils by this prostaglandin. In conclusion, PGD₂ is the most potent inducer of basophil CD203c expression among eicosanoids and may be a key mediator in asthma and other allergic diseases. The balance between DP₁ and DP₂ receptors may be important in determining the magnitude of basophil responses to this prostaglandin.

Address correspondence to: William S. Powell, Meakins-Christie Laboratories, McGill University, 3626 St. Urbain Street, Montreal, Quebec, Canada H2X 2P2. E-mail: william.powell{at}mcgill.ca

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