Abstract
Nitric oxide (NO) plays an important role in the cutaneous response to UV radiation and in cutaneous inflammation. The presence of inducible NO synthase protein in a number of inflammatory dermatoses, coupled with the induction of an intense cutaneous inflammatory infiltrate following topical application of the NO donor-acidified nitrite (NO2(-)), has set the paradigm of NO being an inflammatory mediator in human skin. Using zeolite NO (Ze-NO), a chemically inert, pure NO donor, we have shown that NO per se produces little inflammation. Biologically, relevant doses of Ze-NO induce a dermal CD4-positive T-cell infiltrate and IFN-gamma secretion. In contrast acidified nitrite, releasing equal quantities of NO (measured by dermal microdialysis and cutaneous erythema), induces an intense epidermal infiltrate of macrophages with a similar dermal infiltrate of CD3-, CD4-, CD8-, and CD68-positive cells and neutrophils. Suction blisters were created in Ze-NO-treated and control skin. IFN-gamma, but not IL-4, was detected in Ze-NO-treated skin (mean control 0.1+/-0.07 pg mg(-1) protein, mean IFN-gamma 0.6+/-0.4 pg mg(-1) protein). We suggest that the potent inflammation induced by acidified NO2(-) is secondary to the release of additional mediators.
Publication types
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Clinical Trial
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Research Support, Non-U.S. Gov't
MeSH terms
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Acids
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Administration, Topical
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Blister / chemically induced
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Blister / immunology
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Blister / pathology
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Cell Movement / drug effects
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Cell Movement / immunology
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Dermatitis / immunology*
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Dermatitis / pathology
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Dermatitis / prevention & control*
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Edema / chemically induced
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Edema / immunology
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Edema / pathology
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Epidermis / drug effects
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Epidermis / immunology
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Epidermis / pathology
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Erythema / chemically induced
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Erythema / immunology
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Erythema / pathology
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Female
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Humans
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Inflammation Mediators / administration & dosage
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Inflammation Mediators / adverse effects
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Langerhans Cells / drug effects
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Langerhans Cells / pathology
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Macrophages / drug effects
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Macrophages / pathology
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Male
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Neutrophils / drug effects
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Neutrophils / pathology
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Nitric Oxide / administration & dosage*
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Nitric Oxide / adverse effects*
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Nitric Oxide / immunology
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Nitric Oxide Donors / administration & dosage
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Nitric Oxide Donors / adverse effects
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Skin Ulcer / chemically induced
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Skin Ulcer / immunology
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Skin Ulcer / pathology
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T-Lymphocytes / drug effects*
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T-Lymphocytes / pathology
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Zeolites / administration & dosage
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Zeolites / adverse effects
Substances
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Acids
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Inflammation Mediators
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Nitric Oxide Donors
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Zeolites
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Nitric Oxide