Pneumonocystis carinii pneumonic (PCP) is the most serious infection in patients with AIDS. The infection starts with attachment of the parasite to lung alveolar epithelial cells. P. carinii attachment is therefore an essential step in the establishment of PCP. Yet, little, if anything, is known about the molecular mechanism underlying adherence of P. carinii to host cells. This proposal is based on the discovery that.E carinii expresses a surface lectin that mediates attachment of the parasite to cultured lung epithelial cells in a sugar-inhibitable manner. Accordingly, it is planned to purify and characterize the sugar-binding lectin, raise specific monoclonal and polyclonal antibodies, and determine whether the antibodies as well as lectin-specific saccharides are capable of reversing the binding of P. carinii to its natural substrate, namely, lung alveolar type I cells. It is also planned to clone the gene encoding the lectin, express the lectin gene in bacteria, and determine whether the recombinant lectin competes with the endogenous, P. carinii-bound counterpart, in parasite attachment to epithelial cells. Assessment for a possible role of the lectin in lung injury will be ascertained by determining whether the lectin is cytotoxic to epithelial cells and mitogenic to lymphocytes. In addition to these in vitro experiments, it is proposed to determine whether lectin-specific antibodies and T lymphocytes are effective in reducing infection in the rat model of PCP. The experiments proposed in this grant could very well provide a rational basis for receptor therapy against PCP in patients with AIDS. But even if they don't, they almost certainly will better our understanding of the molecular mechanism governing P. carinii-host interaction.
| Pavia-Ruz, N; Ortega-Barria, E; Alroy, J et al. (1994) A novel in situ model to study Pneumocystis carinii adhesion to lung alveolar epithelial cells. J Immunol Methods 167:161-71 |
| Ortega-Barria, E; Pereira, M E (1992) Identification of a lectin activity in Pneumocystis carinii. Trop Med Parasitol 43:186-90 |
