Applications of anti-curosurf antibodies to understanding the biology of alveolar surfactant.

Abstract

The structure of surfactant-binding proteins from alveolar cell membranes was investigated using monoclonal anti-idiotypic antibodies directed against surfactant-binding regions of anti-surfactant monoclonal antibodies. Two different series of monoclonal anti-surfactant antibodies were used. One series included antibodies against rabbit surfactant, and the other antibodies against porcine surfactant. In addition, two monoclonal anti-idiotype antibodies were made. These anti-idiotype antibodies, called A2R and A2C, bind both anti-Curosurf and anti-rabbit surfactant antibodies comparably. They recognize a 30-kDa cell membrane protein on alveolar and bronchial epithelial cells. In addition, A2C and A2R block the binding of radiolabeled surfactant to these cells. Using a combination of A2C and A2R cDNA expression libraries from both human and porcine lungs were screened. One independent clone was identified in each library that produced protein that bound these monoclonal antibodies. The protein encoded by the cDNA in each clone bound radiolabeled recombinant surfactant protein-A. It is concluded that human and porcine alveolar cell SP-A binding proteins have been identified and its cDNA cloned. The potential implications of this finding for the understanding and treatment of surfactant deficiency states are considerable.