Mittal Anshu, Elmets Craig A, Katiyar Santosh K
Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Photochem Photobiol. 2003 Mar;77(3):259-64. doi: 10.1562/0031-8655(2003)077<0259:ccatms>2.0.co;2.
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.
皮肤暴露于太阳紫外线辐射会引发氧化应激并抑制细胞介导的免疫反应。这些效应与包括光老化和光致癌作用在内的多种皮肤疾病的较高风险相关。我们已经表明，紫外线诱导的浸润白细胞在紫外线照射的皮肤中产生氧化应激方面发挥作用。紫外线诱导的浸润白细胞的高峰期出现在皮肤暴露于紫外线后的48至72小时之间。在本研究中，我们证明了紫外线（90 mJ/cm2）诱导的C3H/HeN小鼠皮肤中的浸润CD11b+细胞是氧化应激的主要来源。过氧化氢（H2O2）被确定为氧化应激的标志物。对活细胞的流式细胞术分析显示，与未暴露于紫外线的皮肤（0.4%）相比，紫外线照射的皮肤中CD11b+H2O2+细胞的数量显著更高（31.8%，P < 0.001）。给C3H/HeN小鼠腹腔注射抗CD11b单克隆抗体（大鼠IgG2b）可抑制紫外线B诱导的白细胞浸润，髓过氧化物酶活性降低（64 - 80%，P < 0.0005）证明了这一点，与注射抗CD11b的大鼠IgG2b同型抗体相比，表皮和真皮中H2O2的产生也显著减少（66 - 83%，P < 0.001 - 0.0005）。此外，在皮肤紫外线照射48小时后获得的全表皮和真皮单细胞悬液中，通过免疫磁珠细胞分离技术分离出CD11b+和CD11b-细胞亚群，并分析其H2O2的产生情况。分析数据显示，与CD11b-细胞群体（占总H2O2的11 - 13%）相比，紫外线照射皮肤中的CD11b+细胞群体在表皮和真皮中产生的总H2O2显著更高（87 - 89%，P < 0.0001）。这些数据表明，浸润的CD11b+细胞是紫外线照射皮肤中氧化应激的主要来源，因此可能在紫外线照射的皮肤中促进光老化和皮肤肿瘤生长。总之，这些数据表明减少紫外线诱导的CD11b+细胞皮肤浸润可能是一种减少太阳紫外线光诱导的氧化应激介导的皮肤疾病（包括光老化和光致癌作用）的替代且有效的策略。
