PNEUMOCYSTIS-CARINII ATTACHMENT INCREASES EXPRESSION OF FIBRONECTIN-BINDING INTEGRINS ON CULTURED LUNG-CELLS

Pneumocystis carinii is an extracellular pathogen which requires attac hment to alveolar epithelial cells for growth and replication. Previou s studies have demonstrated that the extracellular matrix protein fibr onectin (Fn) facilitates attachment of P. carinii to lung cells. This study addresses the role of cell surface Fn receptors (integrins) as m ediators of P. carinii attachment and demonstrates the effect of P. ca rinii attachment on integrin expression on cultured lung cells. To det ermine the role of Fn-binding integrins in P. carinii attachment, atta chment of Cr-51-labelled P. carinii organisms to the lung epithelial c ell line A549 was quantified in the presence or absence of anti-integr in antibodies. Antibodies to the alpha(v) and alpha(5) integrin subuni ts significantly inhibited P. carinii attachment, while addition of an tibody to the alpha subunit of a non-Fn-binding integrin, alpha(2), di d not affect P. carinii attachment. To further investigate the role of Fn-binding integrins in P. carinii attachment, the effect of P. carin ii attachment on expression of the alpha(v) and alpha(5) integrin subu nits was determined. A549 cells incubated with either P. carinii organ isms or with the P. carinii major surface glycoprotein gp120 demonstra ted a 3- to 10-fold increase in expression of the alpha(5) integrin su bunit; however, neither P. carinii nor gp120 affected the expression o f alpha(v) integrin. Furthermore, the effects of P. carinii on A549 ce ll alpha(5) integrin expression were attenuated by the addition of an anti-gp120 antibody which blocks P. carinii attachment to A549 cells. Therefore, P. carinii attachment to lung epithelial cells appears to b e mediated by alpha(v)- and alpha(5)-containing integrins expressed on the epithelial cell surface, and P. carinii attachment results in inc reased expression of the alpha(5) integrin subunit.