Modulation of Pneumocystis carinii adherence to cultured lung cells by a mannose-dependent mechanism.
Pneumocystis carinii is an opportunistic parasite that attaches to the alveolar epithelium during the initiation of pneumonia. It is unknown whether P. carinii recognizes specific receptors on the surface of lung cells. Our study indicates that concanavalin A (Con A), a lectin that recognizes mannose-containing glycoproteins, binds to P. carinii organisms in a saturable manner with a binding affinity of Kd = 11 x 10(-6) mol/L and with 18.5 x 10(6) Con A binding sites per P. carinii organism. Con A binds predominantly to glycoprotein 120, a mannose-rich glycoprotein on the surface of P. carinii. Treatment of cultured target lung cells (A549 cells) with Con A resulted in dramatic reduction of P. carinii attachment, from 34.9% +/- 4.1% to 8.1% +/- 1.3% (p less than 0.001), suggesting that mannose-containing cell surface molecules may be important in P. carinii adherence to target lung cells. In contrast, treatment of P. carinii with Con A resulted in slightly increased adherence of P. carinii when compared with controls. The effects of Con A on P. carinii adherence were reversed when Con A treatments were conducted in the presence of excess mannose, the sugar ligand for Con A. Further, pretreatment of A549 cell monolayers with excess mannose (5000 micrograms/ml) resulted in significant reduction of P. carinii adherence to A549 cells, from 39.4% +/- 2.5% to 28.4% +/- 1.3% (p = 0.003). These studies, for the first time, implicate mannose-containing cell surface molecules as important mediators of attachment between P. carinii and target lung cells.
Limper
A H
AH
Department of Internal Medicine, Mayo Foundation, Rochester, Minnesota.
Pottratz
S T
ST
Martin
W J
WJ
D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000469:parasitology / Q000473:pathology; D000818:Animals; D000946:Antigens, Fungal / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007457:Iodine Radioisotopes; D008168:Lung / Q000187:drug effects / Q000469:parasitology / Q000473:pathology*; D008175:Lung Neoplasms / Q000469:parasitology / Q000473:pathology; D008358:Mannose / Q000378:metabolism / Q000494:pharmacology*; D011010:Pneumocystis / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000469:parasitology / Q000473:pathology
D000946:Antigens, Fungal; D007457:Iodine Radioisotopes; D008358:Mannose