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 ident ified such alveolar cell membrane SP-A-binding proteins using anti-idi otype antibodies directed against the surfactant protein binding regio n of anti-surfactant antibodies. These monoclonal anti-idiotype antibo dies, A2C and A2R, also recognize an alveolar cell membrane protein of almost-equal-to 30 kDa. A pulmonary protein of almost-equal-to 30 kDa binds SP-A. Unique cDNAs encoding this protein were identified in hum an (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 almost-equal-to 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 recepto rs. Their projected structures are consistent with cell membrane recep tors. Recombinant human and porcine SPAR proteins bind SP-A as well as the two anti-idiotype antibodies just as do native lung proteins of a lmost-equal-to 30 kDa. SPAR transcripts are expressed primarily in lun g. 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 expr essing SP-B and SP-C transcripts in appearance, location, and distribu tion. Therefore, cDNAs for pulmonary SP-A-binding proteins from two di sparate species have been isolated and sequenced, and the recombinant proteins they encode bind the same ligand. Further structural, functio nal, and genetic studies of these proteins may help explain how pulmon ary surfactant secretion is regulated.