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

Abstract

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 FcγRI, FcγRII, and FcγRIII, as well as the IgE receptor subtypes FcϵRI and FcϵRII, 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 FcϵRII, as well as for all the Fcγ receptor subtypes, (2) in contrast to unaltered Fcγ subtype expression, however, relative to control human ASM, FcϵRII is significantly up-regulated in inherently asthmatic ASM tissue, (3) up-regulated expression of FcϵRII 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 FcϵRII-induced autologous elaboration of the proinflammatory cytokine, IL-1β, by the atopic sensitized ASM. Conclusion: These observations provide new evidence that human ASM tissue expresses FcϵRII in addition to all 3 subtypes of Fcγ receptors and that the expression of FcϵRII is selectively increased in atopic asthmatic ASM, a phenomenon associated with IgE immune complex/FcϵRII–mediated elaboration of IL-1β by the ASM itself. (J Allergy Clin Immunol 1999;104:575-84.)