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02445 CARRAGUARD PREVENTS MACROPHAGE TRAFFICKING FROM VAGINA - IMPLICATIONS FOR MICROBICIDE DEVELOPMENT Perotti, Marie-Elisa* Considerable evidence suggests that HIV infected macrophages and/or lymphocytes may mediate sexual transmission of HIV. Our laboratory and other laboratories have previously demonstrated that when vitally stained donor mouse lymphocytes or macrophages are placed in the vaginas of mice, some of the stained cells can later be found in the iliac lymph nodes. The aim of this study was to assess the extent of mononuclear cells trafficking from the vagina and to test the possibility that CarraguardTM (PC-515), a vaginal microbicide, would prevent vaginal transmigration of macrophages. When we inoculated mouse mononuclear cells with supravitally stained macrophages; Carraguard TM reduced the number of macrophages in lymph nodes and the spleen by greater than 90%. In contrast, the placebo formulation reduced the number of vitally stained macrophages in the lymph nodes by only 50%. Both formulations were minimally toxic to macrophages over a 4-hour period as compared to no treatment, whereas they were not toxic to human cervical cells. Our findings suggest that CarraguardTM blocks cell trafficking of macrophages from the vaginal vault. Blocking does not appear to result from cytotoxicity. We speculate that blocking cell trafficking may help to prevent sexual transmission of HIV. Marie-Elisa Perotti |
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