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 stimuli and paracrine factors secreted by various dermal cells (lymphocytes, mast-cells, macrophages, fibroblasts) during wounding, cutaneous allergy and infections. We have previously demonstrated that following stimulation with interleukin-4 (IL-4) or interferon-gamma, human EK express 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-alpha from EK. CD23-ligation activates the nitric oxide-dependent pathway, as demonstrated by the high levels of nitrites released in cell supernatants, and the accumulation of intracellular cyclic nucleotides in EK. These second messengers are required for IgE-dependent stimulation of cytokine production by these cells, as this is completely abolished 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.
Bécherel
P A
PA
Molecular Immuno-Hematology Group, CNRS URA 625, Pitié-Salpêtrière Hospital, Paris, France.
Mossalayi
M D
MD
Le Goff
L
L
Ouaaz
F
F
Dugas
B
B
Guillosson
J J
JJ
Debré
P
P
Arock
M
M
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D006152:Cyclic GMP / Q000502:physiology; D000078404:Epidermal Cells; D006801:Humans; D007073:Immunoglobulin E / Q000502:physiology*; D015850:Interleukin-6 / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism / Q000502:physiology*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase; D017455:Receptors, IgE / Q000096:biosynthesis / Q000502:physiology*; D015398:Signal Transduction; D013873:Thionucleotides / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019323:omega-N-Methylarginine
D015850:Interleukin-6; D017455:Receptors, IgE; D013873:Thionucleotides; D014409:Tumor Necrosis Factor-alpha; C016957:adenosine-3',5'-cyclic phosphorothioate; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D007073:Immunoglobulin E; D003994:Bucladesine; D001120:Arginine; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D006152:Cyclic GMP