title: Nitric oxide is toxic to melanocytes in vitro.
abstract: Nitric oxide is a diffusible gaseous mediator generated from l-arginine by inducible and constitutive nitric oxide synthases. It has been associated with cytotoxic effects. Inflammatory cells and Langerhans cells can express the inducible form of nitric oxide synthase and produce large quantities of nitric oxide. The proximity of these cells to melanocytes could result in melanocyte cell death. We studied melanocyte susceptibility to nitric oxide using the nitric oxide donor compound sodium nitroprusside and nitric oxide released by the Langerhans like cell-line XS-52 following stimulation with lipopolysaccharide (LPS). Melanocyte lysis, quantified by chromium release in the presence of sodium nitroprusside was both time and concentration dependent. Co-culture of LPS-stimulated XS cells with melanocytes also resulted in melanocyte cell death. No cell death was observed when melanocytes alone were exposed to LPS. Melanocytes were killed even when the co-cultures were performed across Transwells in which there was no direct contact between XS cells and melanocytes. XS-induced melanocyte death was thus dependent on a diffusible factor consistent with nitric oxide. Cell death was markedly decreased in co-cultures performed in the presence of hemoglobin, a nitric oxide quencher. The possible role that nitric oxide may play in disorders associated with loss of pigmentation is discussed.
authors.affiliation: Cutaneous Biology Research Center, Massachusetts General Hospital, Charlestown, MA, USA.
authors.forename: Aurel O
authors.initials: AO
authors.lastname: Iuga
authors.forename: Abrar A
authors.initials: AA
authors.lastname: Qureshi
authors.forename: Ethan A
authors.initials: EA
authors.lastname: Lerner
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002857:Chromium / Q000032:analysis / Q000378:metabolism; D018920:Coculture Techniques; D004817:Epidermis / Q000187:drug effects; D006454:Hemoglobins / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects; D007801:Langerhans Cells / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008544:Melanocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D009569:Nitric Oxide / Q000378:metabolism / Q000633:toxicity*; D020030:Nitric Oxide Donors / Q000633:toxicity; D009599:Nitroprusside / Q000633:toxicity
chemical_list: D006454:Hemoglobins; D008070:Lipopolysaccharides; D020030:Nitric Oxide Donors; D002857:Chromium; D009599:Nitroprusside; D009569:Nitric Oxide