and Specific Aims.) Pneumocystis carinii is an opportunistic fungus which causes severe pneumonia in immunocompromised hosts including patients with hematologic and solid malignancies, organ transplantation and AIDS. P. carinii has a complex life cycle alternating between cyst and trophozoite forms which live on the epithelium of the lower respiratory tract. Evidence suggests that alveolar macrophages mediate the uptake and removal of P. carinii from alveolar spaces and serve an essential role in host defense against infection. Macrophages not only bind and phagocytize P. carinii, but are further activated to release a number of important inflammatory products including reactive oxidants, arachidonic acid (AA) metabolites and tumor necrosis factor alpha (TNFa). The mechanisms by which macrophages bind and phagocytize P. carinii and become activated to release inflammatory mediators are not well understood. Recent studies suggest that the interaction of macrophages with P. carinii is largely mediated by macrophage mannose receptors. The precise ligand on P. carinii which is recognized by mannose receptors has not been determined. P. carinii, however, contains a mannose-rich surface glycoprotein termed gp120 which is the probable ligand for this receptor. The application hypothesizes that gp120, a principal component of P. carinii, interacts with macrophage mannose receptors and the interaction of gp120 with macrophages mediates P. carinii binding and phagocytosis and activates macrophage inflammatory systems including AA metabolism, oxidant generation, and TNFa release.
The Specific Aims are to: 1) evaluate the interaction of purified gp120 with alveolar macrophages; 2) purify and characterize gp120 receptors present on the surface of alveolar macrophages; 3) evaluated the role of gp120 in mediating the adherence of P. carinii to alveolar macrophages and in initiation of phagocytosis; 4) investigate the role of gp120 in activating macrophage inflammatory systems; and 5) determine the expression of gp120 on isolated P. carinii cysts and trophozoites.
Showing the most recent 10 out of 17 publications
