IGE-DEPENDENT ACTIVATION OF FC-EPSILON-RII CD23(+) NORMAL HUMAN KERATINOCYTES - THE ROLE OF CAMP AND NITRIC-OXIDE/

Epidermal keratinocytes (EK) are exposed to multiple inflammatory stim uli and paracrine factors secreted by various dermal cells (lymphocyte s, mast-cells, macrophages, fibroblasts) during wounding, cutaneous al lergy and infections. We have previously demonstrated that following s timulation with interleukin-4 (IL-4) or interferon-gamma, human EK exp ress the low affinity receptor for IgE (Fc epsilon RII/CD23) on their surface. In the present study, we showed that the ligation of CD23 by IgE/anti-IgE immune complexes or specific monoclonal antibody, induces a dose-dependent release of interleukin-6 and tumor necrosis factor-a lpha from EK. CD23-ligation activates the nitric oxide-dependent pathw ay, as demonstrated by the high levels of nitrites released in cell su pernatants, and the accumulation of intracellular cyclic nucleotides i n EK. These second messengers are required for IgE-dependent stimulati on of cytokine production by these cells, as this is completely abolis hed by cAMP or NO synthase antagonists. Human epithelial keratinocytes may thus participate in IgE-mediated immune responses, through their ability to express functional CD23 antigen.