Role of fibronectin in Pneumocystis carinii attachment to cultured lung cells

Area of Science:

• Microbiology
• Cell Biology
• Immunology

Background:

• Pathogen attachment to host cells is crucial for infection development.
• Pneumocystis carinii (PC) pneumonia involves PC trophozoites attaching to the alveolar epithelium via an unknown mechanism.
• Fibronectin (Fn), an alveolar glycoprotein, mediates cell-cell attachment and pathogen adhesion.

Purpose of the Study:

• To investigate the mechanism of PC trophozoite attachment to alveolar epithelial cells.
• To characterize the binding of fibronectin (Fn) to PC trophozoites.
• To determine if Fn plays a role in PC attachment to host cells.

Main Methods:

• In vitro characterization of 125I-Fn binding to PC trophozoites.
• Inhibition studies using Arg-Gly-Asp-Ser (RGDS) peptide and anti-Fn antibody.
• Quantification of 51Cr-labeled PC trophozoite attachment to an alveolar epithelial cell line.

Main Results:

• Fn binds specifically and saturably to PC trophozoites with a Kd of 1.2 x 10(-8) M.
• RGDS peptide inhibited Fn binding to PC.
• Anti-Fn antibody significantly reduced PC attachment to alveolar cells, an effect reversed by excess Fn.

Conclusions:

• Fn binding to PC trophozoites is likely an initial step in their attachment to alveolar epithelial cells.
• PC recognizes and binds to the RGDS cell-attachment site of Fn.
• This interaction may be a key mechanism in the pathogenesis of Pneumocystis pneumonia.