Altered expression and action of the low-affinity IgE receptor Fc epsilon RII (CD23) in asthmatic airway smooth muscle

Background: Changes in cell surface expression of certain immunoglobulin Fc receptors have been demonstrated in leukocytes isolated from the lungs of atopic asthmatic individuals, This, together with emerging evidence that Fc receptors can also be expressed and activated in non-bone marrow-derived c ell types, including airway smooth muscle (ASM), raises the hypothesis that the atopic asthmatic ASM phenotype is associated with an altered endogenou s expression and action of specific Fc receptors present in the ASM itself. Objective: The current study addressed the above hypothesis by examining (1 ) whether the expression of certain key Fc receptor subtypes for IgE and Ig G is altered in ASM tissue isolated from human atopic asthmatic individuals and (2) whether this altered Fc receptor expression is comparably induced in naive human ASM tissue and cultured cells after their passive sensitizat ion with human atopic asthmatic serum or IgE immune complexes. Methods: Messenger RNA and cell surface protein expression of the individua l IgG receptor subtypes Fc gamma RI, Fc gamma RII, and Fc gamma RIII, as we ll as the IgE receptor subtypes Fc epsilon RI and Fc epsilon RII, were exam ined in human ASM tissue isolated from atopic asthmatic and control (nonato pic/nonasthmatic) individuals. In addition, we examined the effects of pass ive sensitization of ASM tissue and cultured ASM cells with control serum, atopic asthmatic serum, or exogenously administered IgE immune complexes on Fc receptor expression and action (ie, induction of proinflammatory cytoki ne release), Results: The observations demonstrate that (1) human ASM tissue expresses m essenger RNA and surface protein for Fc epsilon RII, as well as for ail the Fcy receptor subtypes, (2) in contrast to unaltered Fc gamma subtype expre ssion, however, relative to control human ASM, FceRII is significantly up-r egulated in inherently asthmatic ASM tissue, (3) up-regulated expression of Fc epsilon RII represents, at least in part, an inducible phenomenon that is largely attributed to IgE immune complex-coupled activation of the recep tor, and (4) the latter action is associated with Fc epsilon RII-induced au tologous elaboration of the proinflammatory cytokine, IL-1 beta, by the ato pic sensitized ASM, Conclusion: These observations provide new evidence that human ASM tissue e xpresses Fc epsilon RII in addition to all 3 subtypes of Fc gamma receptors and that the expression of Fc epsilon RII is selectively increased in atop ic asthmatic ASM, a phenomenon associated with IgE immune complex/Fc epsilo n RII-mediated elaboration of IL-1 beta by the ASM itself.