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 cell types, including airway smooth muscle (ASM), raises the hypothesis that the atopic asthmatic ASM phenotype is associated with an altered endogenous 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 IgG 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 sensitization with human atopic asthmatic serum or IgE immune complexes. Methods: Messenger RNA and cell surface protein expression of the individual IgG receptor subtypes Fc gamma RI, Fc gamma RII, and Fc gamma RIII, as well as the IgE receptor subtypes Fc epsilon RI and Fc epsilon RII, were examined in human ASM tissue isolated from atopic asthmatic and control (nonatopic/nonasthmatic) individuals. In addition, we examined the effects of passive 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 cytokine release), Results: The observations demonstrate that (1) human ASM tissue expresses messenger 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 expression, however, relative to control human ASM, FceRII is significantly up-regulated 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 receptor, and (4) the latter action is associated with Fc epsilon RII-induced autologous elaboration of the proinflammatory cytokine, IL-1 beta, by the atopic sensitized ASM, Conclusion: These observations provide new evidence that human ASM tissue expresses 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 atopic asthmatic ASM, a phenomenon associated with IgE immune complex/Fc epsilon RII-mediated elaboration of IL-1 beta by the ASM itself.
