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SUPERNATANTS FROM THE ULTRAVIOLET-IRRADIATED KERATINOCYTES DECREASE THE RESISTANCE AND DELAYED-TYPE HYPERSENSITIVITY RESPONSE TO MYCOBACTERIUM BOVIS BACILLUS CALMETTE-GUERIN IN MICE AND IMPAIR THE PHAGOCYTIC ABILITY OF MACROPHAGES
Citation:
Jeevan, A., S. Ullrich, V. Dizon, AND M. Kripke. SUPERNATANTS FROM THE ULTRAVIOLET-IRRADIATED KERATINOCYTES DECREASE THE RESISTANCE AND DELAYED-TYPE HYPERSENSITIVITY RESPONSE TO MYCOBACTERIUM BOVIS BACILLUS CALMETTE-GUERIN IN MICE AND IMPAIR THE PHAGOCYTIC ABILITY OF MACROPHAGES. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-93/096 (NTIS PB93175651), 1992.
Description:
Recently, we demonstrated that exposure of mice to a single high does or to multiple smaller doses of ultraviolet (UV) radiation decreased the induction of the delayed type hypersensitivity (DTH) response to Mycobacterium bovis-BCG injected into unexposed sites. In view of the limited ability of UV radiation to penetrate beyond the epidermis and upper layers of the dermis it is not entirely clear how exposing the dorsal skin of mice to UV radiation can cause an systemic impairment of the immune response to BCG. In this study we report that mic, injected with supernatants from keratinocytes cultures exposed to UV radiation induced impairments in host resistance to BCG. Both the induction and the elicitation of the delayed type hypersensitivity (DTH) reaction was suppressed following the intravenous injection of supernatants from the UV-irradiated keratinocytes, in a dose-dependent manner. Furthermore, injecting supernatants from the UV-irradiated keratinocytes interfered with the elimination of viable bacteria from the lymphoid organs. In order to determine whether macrophages were the target of the UV-induced keratinocyte-derived suppressive cytokine, macrophages were isolated from mice injected with the suppressive cytokine and the uptake and intracellular killing of BCG in vitro was studied. The suppressive factor significantly reduced the uptake of BCG by the macrophage but not the rate of intracellular killing. These findings suggest that the suppressive cytokine interferes with the elimination of bacterial in vivo by interfering with the initial step in bacterial clearance, uptake of the bacteria by host macrophages. These results indicate that soluble mediators released from UV-irradiated keratinocytes may be involved in the UV-induced systemic suppression of immunity to BCG and they may act by interfering with certain macrophage functions.
