Surfactant protein A-binding proteins. Characterization and structures.

An alveolar cell membrane protein acts as a surfactant protein A (SP-A) receptor; it binds SP-A and regulates surfactant secretion. We identified such alveolar cell membrane SP-A-binding proteins using anti-idiotype antibodies directed against the surfactant protein binding region of anti-surfactant antibodies. These monoclonal anti-idiotype antibodies, A2C and A2R, also recognize an alveolar cell membrane protein of approximately 30 kDa. A pulmonary protein of approximately 30 kDa binds SP-A. Unique cDNAs encoding this protein were identified in human (4.1-kilobase) and porcine (1.8-kilobase) lung expression libraries. Coding regions of these cDNAs cross-hybridize with each other under stringent conditions. Both cDNAs encode similar approximately 32-kDa proteins that bind SP-A. The human and porcine SP-A recognition (SPAR) proteins resemble each other, as well as other cell membrane receptors. Their projected structures are consistent with cell membrane receptors. Recombinant human and porcine SPAR proteins bind SP-A as well as the two anti-idiotype antibodies just as do native lung proteins of approximately 30 kDa. SPAR transcripts are expressed primarily in lung. The cellular distribution of these transcripts, as determined by in situ hybridization, is similar to that of SPAR protein, as determined by immunohistochemistry; both are found in cells consistent with type II pneumocytes. SPAR-producing cells resemble the alveolar cells expressing SP-B and SP-C transcripts in appearance, location, and distribution. Therefore, cDNAs for pulmonary SP-A-binding proteins from two disparate species have been isolated and sequenced, and the recombinant proteins they encode bind the same ligand. Further structural, functional, and genetic studies of these proteins may help explain how pulmonary surfactant secretion is regulated.