TB PLEURISY &MONOCYTE TRANSMIGRATION IN AIDS

Indiana Univ-Purdue Univ At Indianapolis, Indianapolis IN

Investigators

Linked publications & trials

Abstract

DESCRIPTION (Adapted from the Investigator's Abstract): Infection with Mycobacterium tuberculosis and pleurisy caused by M. tuberculosis are endemic in patients with AIDS. Tuberculous pleural effusions typically contain large numbers of monocytes and have high protein concentrations. Patients with AIDS have low monocyte counts and M. tuberculosis often disseminates. However, the regulatory mechanism controlling movements of monocytes and protein into the pleural space across the mesothelium are unknown. Tuberculous pleural effusions contain C-C chemokines, which are chemotactic for monocytes. Activated mesothelial cells release C-C chemokines and so may play a pivotal role in recruitment of monocytes to the pleural space. Mesothelial cells also express adhesion molecules that interact with monocyte glycoproteins. The investigators will use an in vitro system to investigate these mechanisms, analyzing movement of monocytes across mesothelial monolayer. The investigators hypothesize that transmigration of monocytes across the mesothelium depends on the establishment of chemotactic gradients, on the expression of adhesion molecules, and on changes in pleural permeability to macromolecules. The investigators will test the hypothesis with four specific aims examining transmigration of monocytes across mesothelial cell monolayers: (1) to evaluate whether C-C chemokines cause transmigration; (2) to evaluate how Th1 and Th2 cytokines affect transmigration; (3) to evaluate whether mesothelial expression of adhesion molecules is essential for transmigration; and (4) to evaluate whether monocyte transmigration is associated with changes in mesothelial permeability.