Pneumocystis carinii attachment increases expression of fibronectin-binding integrins on cultured lung cells.
Pneumocystis carinii is an extracellular pathogen which requires attachment to alveolar epithelial cells for growth and replication. Previous studies have demonstrated that the extracellular matrix protein fibronectin (Fn) facilitates attachment of P. carinii to lung cells. This study addresses the role of cell surface Fn receptors (integrins) as mediators of P. carinii attachment and demonstrates the effect of P. carinii attachment on integrin expression on cultured lung cells. To determine the role of Fn-binding integrins in P. carinii attachment, attachment of 51Cr-labelled P. carinii organisms to the lung epithelial cell line A549 was quantified in the presence or absence of anti-integrin antibodies. Antibodies to the alpha v and alpha 5 integrin subunits significantly inhibited P. carinii attachment, while addition of antibody to the alpha subunit of a non-Fn-binding integrin, alpha 2, did not affect P. carinii attachment. To further investigate the role of Fn-binding integrins in P. carinii attachment, the effect of P. carinii attachment on expression of the alpha v and alpha 5 integrin subunits was determined. A549 cells incubated with either P. carinii organisms or with the P. carinii major surface glycoprotein gp120 demonstrated a 3- to 10-fold increase in expression of the alpha 5 integrin subunit; however, neither P. carinii nor gp120 affected the expression of alpha v integrin. Furthermore, the effects of P. carinii on A549 cell 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 be mediated by alpha v- and alpha 5-containing integrins expressed on the epithelial cell surface, and P. carinii attachment results in increased expression of the alpha 5 integrin subunit.
Department of Internal Medicine, Indiana University School of Medicine, Indianapolis.
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Pottratz
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Weir
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Wisniowski
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D005353:Fibronectins / Q000378:metabolism*; D005656:Fungal Proteins / Q000494:pharmacology; D006801:Humans; D039482:Integrin alpha5; D039564:Integrin alphaV; D016023:Integrins / Q000096:biosynthesis*; D008168:Lung / Q000166:cytology / Q000382:microbiology* / Q000502:physiology; D011010:Pneumocystis / Q000502:physiology*; D011020:Pneumonia, Pneumocystis / Q000382:microbiology; D011485:Protein Binding; D051381:Rats; D017469:Receptors, Fibronectin / Q000378:metabolism
D015703:Antigens, CD; D005353:Fibronectins; D005656:Fungal Proteins; D039482:Integrin alpha5; D039564:Integrin alphaV; D016023:Integrins; D017469:Receptors, Fibronectin