Pneumocystis carinii (PC) pneumonia is a frequent cause of morbidity and mortality in immunosuppressed individuals, especially in those with HIV infection. Attachment of PC organisms to the alveolar epithelium with subsequent damage to the epithelial cell barrier is a pathologic hallmark of PC pneumonia. Alveolar epithelial cells produce the multi-functional cytokine interleukin-6 (IL-6) in response to a variety of stimuli. Recent investigations have examined the role of the cell adhesive proteins fibronectin (Fn) and vitronectin (Vn) as well as their respective cell surface receptors in the attachment of PC to lung cells. IL-6 is known to increase cellular expression of Fn, Vn and integrins. Our proposal is based on the hypothesis that PC attachment to alveolar epithelial cells results in epithelial cell production of IL-6 which then acts on the alveolar epithelium in a paracrine fashion to increase local production of Fn and Vn as well as increase cell surface expression of Fn- and Vn- binding integrins. Increased expression of these cell adhesive proteins would provide more sites of attachment for PC organisms and allow for amplification of the infection. To test this hypothesis we have developed the following four specific aims: l) To determine whether PC and its major surface glycoprotein (gpl20) induce IL-6 secretion and changes in IL-6 mRNA expression in A549 cells and primary cultures of rat alveolar epithelial cells; 2) To determine whether the effect of PC on alveolar epithelial cell IL-6 expression requires attachment of PC organisms to the alveolar epithelial cells; 3) To determine the effect of IL-6 on PC attachment to alveolar epithelial cells; 4) To determine the effect of IL- 6 on production of Fn and Vn and expression of cell surface Fn- and Vn- binding integrins (alpha5, alpha-v, beta1, beta3, beta5 and beta6) on alveolar epithelial cells.
| Pottratz, S T (1998) Pneumocystis carinii interactions with respiratory epithelium. Semin Respir Infect 13:323-9 |
| Pottratz, S T; Reese, S; Sheldon, J L (1998) Pneumocystis carinii induces interleukin 6 production by an alveolar epithelial cell line. Eur J Clin Invest 28:424-9 |
