VAGINAL SURFACTANT PROTEIN-A: MODULATION OF MACROPHAGE ACTIVITY

Pennsylvania State Univ Hershey Med Ctr, Hershey PA

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Abstract

Vulvovaginal inflammatory conditions and their sequelae have a tremendous impact on public health, being implicated in disorders ranging from preterm labor to sexually transmitted disease. Though these conditions are thought to involve abnormalities of host defense, there is very little known about lower genital tract host defense mechanisms. Cyclic vulvovaginitis (CVV), a recurring vulvar and vaginal inflammatory condition, provides a propitious setting in which to explore alterations in host defense. This study is based on a novel observation that surfactant protein-A (SP-A), usually associated with lung physiology, is also present in human vaginal fluid. This observation has special relevance to CVV, as there is growing evidence that SP-A plays a role in pulmonary host defense by modulating macrophage phagocytosis and cytokine production. Of direct relevance to this study is evidence that SP-A enhances phagocytosis by alveolar macrophages and that in the vagina, as in the lung, macrophages are a major component of host defense. These findings lead the investigators to postulate that vaginal SP-A participates in host response to vaginal infection by modulation of macrophage phagocytosis and inflammatory cytokine production. This hypothesis will be tested using differential THP-1 cells, a well characterized model for macrophages. Vaginal lavage fluid will be added to THP-1 cells and then assay changes in macrophage phagocytosis of vaginal pathogens and macrophage production of proinflammatory cytokines will be determined. We will first define normal vaginal SP-A levels and macrophage activating activity in healthy women, then test the hypothesis that vaginal SP-A increases macrophage activity during recurrence of CVV. These studies will establish a functional assay for vaginal host-defense mediators. Moreover, if this hypothesis is proven, they will ultimately lead to a change in the prevention and treatment of lower genital tract infections and their inflammatory sequelea.