Pneumocystis carinii attachment to cultured lung cells by pneumocystis gp 120, a fibronectin binding protein.

Abstract

Pneumocystis carinji is an extracellular organism which is thought to require attachment to alveolar epithelial cells for its growth and replication in humans. Fibronectin (Fn) binding to P. carinji is essential for optimal P. carinfi attachment. This study demonstrates that gp120, a 110-120-kD membrane glycoprotein on P. carinji, mediates attachment of the organism to cultured lung cells and is the site of Fn binding to P. carinji. A "Cr-labeled P. carinfi binding assay was used to quantify attachment of the organism to the alveolar epithelial cell line A549. Addition of free gpl20, purified from whole P. carinji organisms, caused a significant decrease in attachment of P. carinti to A549 cells from 44.2±5.5% to 22.4±4.2% (P < 0.01). Preincubation of the P. carinii organisms with a polyclonal antibody to gpl20 also resulted in a marked decrease in P. carinji attachment to A549 cells from 46.8%±5.2% to 213±4.8% (P < 0.01). Furthermore, addition of free gp120 to P. carinfi organisms caused a significant reduction in specific binding of 125I-Fn to P. carinli (from 83.3±8.5 ng to 47.1±5.9 ng, P < 0.01). Similarly, anti-gpl20 antibody decreased specific Fn binding to P. carinfi from 74.3±8.4 ng to 25.5±5.3 ng (P < 0.001). Solubilized P. carriim organisms separated by gel electrophoresis and blotted with "'I-Fn demonstrated specific binding of the '2'I-Fn to gpl20. In addition, a specific anti-#,-integrin antiserum reacted with gpl20 by Western blot, suggesting structural homology between gpl20 and the t-subunit of integrins. Thus, the data suggest that the P. carinii membrane glycoprotein gpl20 functions as a Fn binding protein and is required for optimal P. carinji attachment to alveolar epithelial cells. (J. Clin. Invest. 1991. 88:403-407.)

Reduced binding and phagocytosis of Pneumocystis carinii by alveolar macrophages from persons infected with HIV-1 correlates with mannose receptor downregulation.

“…Normal human and rodent alveolar macrophages are capable of binding and phagocytosis of P . carinii (12, [14][15][16][17][18], and phagocytosis results in rapid elimination of the organisms. Binding may in part be mediated via fibronectin (16), and phagocytosis may be facilitated by immunoglobulin (14,18).…”

Host Cell Invasion by Medically Important Fungi

“…jirovecii is an important cause of pneumonia in immunocompromised hosts, but rarely disseminates beyond the pulmonary system. Like other pathogenic fungi, P. jirovecii adheres well to pulmonary epithelial cells (Pottratz and Martin 1990a,b;Pottratz et al 1991). However, this fungus does not invade these cells to any significant degree and intracellular fungi are observed only within macrophages and granulocytes (Hoyte et al 1997;Limper et al 1997).…”

“…However, this fungus does not invade these cells to any significant degree and intracellular fungi are observed only within macrophages and granulocytes (Hoyte et al 1997;Limper et al 1997). The adherence of P. jirovecii to epithelial cells is mediated through the binding of the extracellular macromolecules fibronectin and vitronectin, which serve as bridging molecules linking the fungus to host cells (Pottratz and Martin 1990b;Pottratz et al 1991Pottratz et al , 1994Limper et al 1993). Vitronectin and fibronectin both interact with b-glucans on the surface of the fungus (Vassallo et al 2001), and fibronectin is also bound by the major surface glycoprotein ( previously termed gp120) of P. jirovecii (Pottratz et al 1991).…”

“…The adherence of P. jirovecii to epithelial cells is mediated through the binding of the extracellular macromolecules fibronectin and vitronectin, which serve as bridging molecules linking the fungus to host cells (Pottratz and Martin 1990b;Pottratz et al 1991Pottratz et al , 1994Limper et al 1993). Vitronectin and fibronectin both interact with b-glucans on the surface of the fungus (Vassallo et al 2001), and fibronectin is also bound by the major surface glycoprotein ( previously termed gp120) of P. jirovecii (Pottratz et al 1991). Heterologous expression of this major surface glycoprotein in the yeast S. cerevisiae enhances the adherence of this organism to epithelial cells, highlighting the importance of this glycoprotein in adhesion (Kutty et al 2013).…”

Basic biology of Pneumocystis carinii: a mini review

“…At some points such contact was done through filopodium-like structures. There are evidences that fibronectin is a mediator of the P. carinii attachment to pneumocytes with the participation of fibronectin-binding receptor on the fungus surface and a fibronectin-binding integrin of the host cell surface (Pottratz et al 1991, 1994, Aliouat et al 1993.…”