AUTOLOGOUSLY UP-REGULATED FC RECEPTOR EXPRESSION AND ACTION IN AIRWAYSMOOTH-MUSCLE MEDIATES ITS ALTERED RESPONSIVENESS IN THE ATOPIC ASTHMATIC SENSITIZED STATE

To elucidate the role of IgE dependent mechanisms in inducing altered airway responsiveness in the atopic asthmatic state, the expression an d actions of Fc receptor activation were examined in isolated rabbit t racheal smooth muscle (TSM) tissue and cultured cells passively sensit ized with sera from atopic asthmatic patients or nonatopic/nonasthmati c (control) subjects. Relative to control tissues, the atopic asthmati c-sensitized TSM exhibited significantly increased maximal isometric c ontractility to acetylcholine (P < 0.01) and attenuated maximal relaxa tion responses and sensitivity (i.e., -log ED50) to isoproterenol (P < 0.005),These changes in agonist responsiveness in atopic sensitized T SM were ablated by pretreating the tissues with a blocking mAb to the low affinity receptor for IgE, Fc epsilon RII (i.e., CD23) or by deple ting the sensitizing serum of its immune complexes. Moreover, in compl imentary experiments, exogenous administration of IgE immune complexes to naive TSM produced changes in agonist responsiveness that were qua litatively similar to those obtained in the atopic asthmatic-sensitize d state. Extended studies further demonstrated that, in contrast to th eir respective controls, atopic asthmatic serum-sensitized human and r abbit TSM tissue and cultured cells exhibited markedly induced mRNA an d cell surface expression of Fc epsilon RII, whereas constitutive expr ession of the IgG receptor subtype, Fc gamma RIII, was unaltered, Fina lly, the up-regulated mRNA expression of Fc epsilon RII observed follo wing exposure of TSM to atopic asthmatic serum or to exogenously admin istered IgE immune complexes was significantly inhibited by pretreatin g the tissues or cells with anti-CD23 mAb, Collectively, these observa tions provide evidence demonstrating that the altered agonist responsi veness in atopic asthmatic sensitized airway smooth muscle is largely attributed to IgE-mediated induction of the autologous expression and activation of Fc epsilon RII receptors in the airway smooth muscle its elf.