Expression and glucocorticoid regulation of surfactant protein C in human fetal lung

The hydrophobic surfactant protein C (SP-C) is known to modulate the biophysical properties of surfactant phospholipid. Although SP-C mRNA has been demonstrated in human fetal lung, there is limited information regarding developmental expression and processing of proSP-C protein. Two epitope-specific human proSP-C antisera, anti-hCPROSP-C (His(59)-Ser(72)) and anti-hCTERMSP-C (Gly(162)-Gly(175)), were generated to complement previously produced anti-NPROSP-C (Met(10)-Gln(23)) for the study of proSP-C expression in human fetal lung. Western blotting and immunocytochemistry detected expression of proSP-C protein by 12-16 wk of gestation. ProSP-C immunoreactivity of preculture lung, limited to expression of proSP-C-21 in airway epithelial cells, was markedly enhanced by culture of lung explants in dexamethasone. To examine synthesis of proSP-C, homogenates from explants were labeled with S-35-Met/Cys for 0.5-4 h. Immunoprecipitation with anti-NPROSP-C detected S-35-proSP-C-21 by 30 min and, after 2 h of labeling, there was a 15-fold increase in S-35-proSP-C-21 in dexamethasone treated lungs versus controls. Synthesis of proSP-C-21 was followed by the appearance of a 24-kD form and smaller processing intermediates including 6-10-kD forms. Posttranslational processing of proSP-C-21 was not observed in control explants. SP-C6-10 were not recognized by either anti-CPROSP-C or anti-hCTERMSP-C. These results indicate that low level expression of proSP-C protein first occurs in epithelial cells early in the second trimester and that expression can be enhanced by dexamethasone. Initial posttranslational processing of human proSP-C involves modification of proSP-C-21 to SP-C-24 and subsequent proteolysis of C-terminal propeptide domains. We speculate that absence of low M-r intermediates in unstimulated second trimester fetal lung tissue reflects developmental and glucocorticoid dependent regulation of proSP-C-21 synthesis and posttranslational processing.