INVOLVEMENT OF CYCLIC-AMP AND NITRIC-OXIDE IN IMMUNOGLOBULIN E-DEPENDENT ACTIVATION OF FC-EPSILON-RII CD23(+) NORMAL HUMAN KERATINOCYTES/

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 after stim ulation with interleukin 4 or interferon-gamma, human EK express the l ow-affinity receptor for IgE (Fc epsilon RII/CD23) on their surface. I n the present study, we showed that the ligation of CD23 by IgE/anti-I gE immune complexes or specific monoclonal antibody induces a dose-dep endent release of interleukin 6 and tumor necrosis factor-cu from EK. CD23-ligation activates the nitric oxide-dependent pathway, as demonst rated by the high levels of nitrites released in cell supernatants, an d the accumulation of intracellular cyclic nucleotides in EK. These se cond messengers are required for IgE-dependent stimulation of cytokine production by these cells, inasmuch as this is completely abolished b y the use of cAMP or nitric oxide synthase antagonists. Human epitheli al keratinocytes may thus participate in IgE-mediated immune responses , through their ability to express functional CD23 antigen.