title: CD11b+ cells are the major source of oxidative stress in UV radiation-irradiated skin: possible role in photoaging and photocarcinogenesis.
abstract: Exposure of skin to solar UV radiation induces oxidative stress and suppression of cell-mediated immune responses. These effects are associated with the greater risk of several skin disorders including photoaging and photocarcinogenesis. We have shown that UV-induced infiltrating leukocytes contribute in developing oxidative stress in UV-irradiated skin. The peak period of UV-induced infiltrating leukocytes lies between 48 and 72 h after UV exposure of the skin. In this study we demonstrated that UV (90 mJ/cm2)-induced infiltrating CD11b+ cells in C3H/HeN mice skin were the major source of oxidative stress. Hydrogen peroxide (H2O2) was determined as a marker of oxidative stress. Flow cytometric analysis of viable cells revealed that the number of CD11b+H2O2+ cells were significantly higher (31.8%, P < 0.001) in UV-irradiated skin in comparison with non-UV-exposed skin (0.4%). Intraperitoneal administration of monoclonal antibodies to CD11b (rat IgG2b) to C3H/HeN mice inhibited UVB-induced infiltration of leukocytes, as evidenced by reduction in myeloperoxidase activity (64-80%, P < 0.0005), concomitant with significant reduction in H2O2 production both in epidermis and dermis (66-83%, P < 0.001-0.0005) when compared with the administration of rat IgG2b isotype of anti-CD11b. Furthermore, CD11b+ and CD11b- cell subsets were separated by immunomagnetic cell isolation technique from total epidermal and dermal single cell suspensions obtained 48 h after UV irradiation of the skin and analyzed for H2O2 production. Analytical data revealed that CD11b+ cell population from UV-irradiated skin resulted in significantly higher production of total H2O2 in both epidermis and dermis (87-89%, P < 0.0001) in comparison with CD11b- cell population (11-13% of total H2O2). These data revealed that infiltrating CD11b+ cells were the major source of oxidative stress in UV-irradiated skin and thus may contribute to photoaging and promotion of skin tumor growth within the UV-irradiated skin. Together, these data suggest that reduction in UV-induced skin infiltration of CD11b+ cells may be an alternative and effective strategy to reduce solar UV light-induced oxidative stress-mediated skin disorders including photoaging and photocarcinogenesis.
authors.affiliation: Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Anshu
authors.initials: A
authors.lastname: Mittal
authors.forename: Craig A
authors.initials: CA
authors.lastname: Elmets
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Katiyar
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D005260:Female; D051379:Mice; D008809:Mice, Inbred C3H; D018384:Oxidative Stress; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects*; D015595:Skin Aging / Q000276:immunology / Q000528:radiation effects; D012878:Skin Neoplasms / Q000209:etiology; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D039481:CD11b Antigen