Receptor-mediated regulation of pulmonary surfactant secretion

Surfactant protein A (SP-A) regulates surfactant secretion via an SP-A specific type II cell membrane receptor (SPAR). We report here that two anti-SPAR monoclonal antibodies can modulate the secretory inhibition caused by SP-A. A2C and A2R are rat monoclonal antibodies raised independently and recognize a 32-kDa protein on rat alveolar type II cell membranes. Immunocytochemical studies show that these antibodies bind to isolated type II cells. Scatchard analysis confirms that SP-A binds alveolar type II cells through a single affinity receptor and shows that A2C and A2R recognize that same receptor. Both antibodies inhibit the binding of 125I-SP-A to isolated type II cells. The functional activity of this 32-kDa protein was studied by examining surfactant secretion in isolated type II cells. Surfactant phospholipid secretion was measured in cells that were exposed to various surfactant phospholipid secretagogues (ATP, dibutyryl cAMP, terbutaline, or ionomycin), +/-SP-A (100 ng/ml), +/-A2C or A2R. Both antibodies block the negative feedback loop by which SP-A inhibits surfactant secretion. This activity of A2C and A2R is dose-dependent and is independent of the secretagogue used. Thus, the 32-kDa type II cell membrane protein bound by A2C and A2R is the functional receptor on alveolar type II cell membranes and regulates type II cell surfactant secretion.