Effects of prostaglandin D(2) and 5-lipoxygenase products on the expression of CD203c and CD11b by basophils.

Abstract

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 D(2) (PGD(2); EC(50), 10 nM) was by far the most potent activator of CD203c expression, with other prostanoids having little effect. This response was mediated by the DP(2) receptor/chemoattractant receptor-homologous molecule expressed on Th2 cells because it was shared by the selective agonist 15R-methyl-PGD(2) (EC(50), 3 nM). The 5-lipoxygenase products leuko-triene B(4) and 5-oxo-6,8,11,14-eicosatetraenoic acid also stimulated CD203c expression but to a lesser extent than PGD(2), whereas leukotriene D(4) was inactive. Neither PGD(2) nor 5-oxo-6,8,11,14-eicosatetraenoic acid stimulated histamine release or CD63 expression on basophils. Both PGE(2) and the DP(1) receptor agonist BW245C [(4S)-(3-[(3R,S)-3-cyclohexyl-3-hydroxypropyl]-2,5-dioxo)-4-imidazolidineheptanoic acid] strongly inhibited DP(2) receptor-mediated CD203c expression. The DP(1) receptor antagonist BWA868C [3-[(2-cyclohexyl-2-hydroxyethyl)amino]-2,5-dioxo-1-(phenylmethyl)-4-imidazolidine-heptanoic acid] enhanced PGD(2)-induced CD203c expression, suggesting that interaction of PGD(2) with DP(1) receptors can limit activation of basophils by this prostaglandin. In conclusion, PGD(2) 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 DP(1) and DP(2) receptors may be important in determining the magnitude of basophil responses to this prostaglandin.