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 immunocompromised patients. Previous work has shown that fibronectin (Fn) and Fn-binding integrins mediate PC attachment to lung cells in vitro. Gamma-interferon (gamma-IFN) is a major factor in host defence against PC infection. To determine the effect of gamma-IFN on PC attachment to lung cells, the alveolar epithelial cell line A549 was incubated with gamma-IFN (0-10(4) U mL(-1)) and attachment of 51Cr-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 observed after 24 h and reached a maximum after 48 h of incubation. To investigate the mechanism of this decrease, we examined integrin expression on gamma-IFN-treated A549 cells. A549 cell expression of the alpha5 and beta1 integrin subunits was decreased, whereas expression of the alpha(v) subunit was unchanged. Northern blot analysis showed a similar decrease in mRNA for the alpha5 and beta1 integrins. Therefore, gamma-IFN-mediated inhibition of PC infection may, in part, result from inhibition of PC attachment to alveolar epithelial cells caused by gamma-IFN-induced decreases in alveolar integrin expression.
Pottratz
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ST
Division of Pulmonary and Critical Care, Indiana University School of Medicine, Indianapolis 46202, USA.
Weir
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D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D002460:Cell Line; D004847:Epithelial Cells; D005260:Female; D016023:Integrins / Q000096:biosynthesis* / Q000378:metabolism* / Q000502:physiology; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology*; D008168:Lung / Q000166:cytology* / Q000187:drug effects / Q000382:microbiology; D011010:Pneumocystis / Q000187:drug effects* / Q000276:immunology; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D016023:Integrins; D007371:Interferon-gamma