Pneumocystis carinii attachment increases expression of fibronectin-binding integrins on cultured lung cells

Abstract

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.

Pneumocystis carinii induces interleukin 6 production by an alveolar epithelial cell line

“…The direct effects of PC on alveolar epithelial cell function have not been thoroughly investigated. Recent studies from our laboratory have demonstrated PC-induced changes in lung cell integrin expression [35] that may play a role in the pathogenesis of PC pneumonia. Our current study gives further evidence for a role of alveolar epithelial cell-derived factors in the response to PC infection.…”

Effect on parasite eradication ofPneumocystis carinii-specific antibodies produced in the presence or absence of CD4+ α β T lymphocytes

“…Enhanced phagocytosis due to P. carinii opsonization with specific Ab to surface structures [30,31] may be only one possible consequence. Blocking surface molecules such as vitronectin-and fibronectin-binding integrins, which are important for P. carinii attachment to host cells [32][33][34][35], could also impede parasite growth. Furthermore, host cell injury as a consequence of parasite adherence [36,37] could be prevented by these Ab.…”

XVI. The Pneumocystis carinii major surface glycoprotein (MSG): its potential involvement in the pathophysiology of pneumocystosis

“…Cell surface ¢bronectin binding receptors of the integrin family have been identi¢ed. Pottratz et al showed that antibodies towards the ¢bronectin binding K v and K S integrin subunits signi¢cantly inhibited attachment of whole organisms [19]. Further, rat P. carinii organisms and MSG upregulated the expression of K S integrin subunits on A549 cells, and anti-MSG antibody attenuated K S integrin expression, suggesting that MSG is involved in upregulation and expression of molecules that mediates organism-cell attachment.…”