GAMMA-INTERFERON INHIBITS PNEUMOCYSTIS-CARINII ATTACHMENT TO LUNG-CELLS BY DECREASING EXPRESSION OF LUNG CELL-SURFACE INTEGRINS

Pneumocystis carinii (PC) is a leading cause of pneumonia in immunocom promised patients. Previous work has shown that fibronectin (Fn) and F n-binding integrins mediate PC attachment to lung cells in vitro. Gamm a-interferon (gamma-IFN) is a major factor in host defence against PC infection. To determine the effect of gamma-IFN on PC attachment to lu ng cells, the alveolar epithelial cell line A549 was incubated with ga mma-IFN (0-10(4) U mL(-1)) and attachment of Cr-51-labelled PC to the A549 cells was quantified. PC attachment was significantly decreased ( P<0.01) by addition of gamma-IFN with no evidence of injury to either the PC or A549 cells. Effects of gamma-IFN on PC attachment were obser ved after 24 h and reached a maximum after 48 h of incubation. To inve stigate the mechanism of this decrease, we examined integrin expressio n on gamma-IFN-treated A549 cells. A549 cell expression of the alpha(5 ) and beta(1) integrin subunits was decreased, whereas expression of t he alpha(v) subunit was unchanged. Northern blot analysis showed a sim ilar decrease in mRNA for the alpha(5) and beta(1) integrins. Therefor e, gamma-IFN-mediated inhibition of PC infection may, in part, result from inhibition of PC attachment to alveolar epithelial cells caused b y gamma-IFN-induced decreases in alveolar integrin expression.