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Carrageenan Formulation Prevents Macrophage Trafficking from Vagina: Implications for Microbicide Development¹

Department of General Physiology and Biochemistry,³ University of Milan, Milan, Italy The Population Council,⁴ New York, New York 10021

Considerable evidence suggests that human immunodeficiency virus (HIV)-infected macrophages and/or lymphocytes may mediate sexual transmission of HIV. We and others 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 cell trafficking from the vagina and to test the possibility that carrageenan formulation, a sulfated polysaccharide formulation containing 3% PDR98-15 carrageenan (PC-515; FMC Biopolymer, Rockland, ME), a vaginal microbicide, would prevent vaginal transmigration of macrophages. When supravitally stained mouse macrophages and T cells were inoculated into the vagina of recipient mice, discrete numbers of donor cells migrated to the recipient iliac and inguinal lymph nodes and spleen. When recipient mice were preinoculated with the carrageenan formulation, the number of macrophages in lymph nodes and spleen was reduced by >90%. In contrast, a methylcellulose formulation, which is believed to be inactive, did not significantly reduce migration to the lymphoid organs. Our findings suggest that the carrageenan formulation blocks cell trafficking of macrophages from vagina and that blocking does not result from cytotoxicity. Blocking cell trafficking may help to prevent sexual transmission of HIV.

¹ This work was supported by NICHD grant HD41752, NIAID grant AI37793, The Rockefeller Foundation, and grants from MIUR/University of Milan.

² Correspondence: David M. Phillips, The Population Council, 1230 York Ave., New York, NY 10021. FAX: 212 327 7678; dphillips{at}popcouncil.org

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