ISOLATION AND PARTIAL CHARACTERIZATION OF A RECEPTOR TO SURFACTANT PROTEIN-A EXPRESSED BY RAT TYPE-II PNEUMOCYTES

Surfactant protein A (SP-A), the most abundant protein component in pu lmonary surfactant, has been shown to enhance surfactant phospholipid uptake by the type II alveolar epithelial cell. Recent evidence has sh own that this process may be receptor-mediated. We undertook this stud y to isolate the putative receptor from type II cell membranes. We iso lated two specific SP-A binding proteins from type II cells with appar ent molecular weights (M-r) of 86 and >200 kD under nonreducing condit ions. Under reducing conditions, the higher-M-r protein was not presen t, but three proteins with apparent M-r of 65, 55, and 50 kD were visi ble, in addition to the 86-kD protein, indicating that the higher-M-r protein was composed of the smaller peptides which form disulfide bond s. The 86-kD protein is a glycoprotein with similar to 30% of its mass as carbohydrate. The 50-kD protein is also a glycoprotein (similar to 30% of its mass as carbohydrate), and SP-A binds to the protein core. Polyclonal and monoclonal antibodies to these peptides saturably bind to the surface of type II cells but not other lung cells, as shown by immunohistochemistry. SP-A competitively inhibits binding of one mono clonal antibody to type II cells, and the monoclonal antibody was able to block the effect of SP-A on phospholipid uptake by type II cells, indicating that this complex is a receptor to SP-A which is expressed on type II cells. This novel receptor is fundamental to the biology of surfactant metabolism in the lung.