Developmental changes of neutral glycosphingolipids as receptors for pulmonary surfactant protein SP-A in the alveolar epithelium of murine lung

A dramatic change in the glycosphingolipid composition in murine lung occurred between 1 day and 1 week after birth. GlcCer and LacCer were the predominant neutral glycosphingolipids prenatally and 1 day after birth, and the concentrations of globo- and ganglio-series glycosphingolipids increased abruptly from 1 week after birth, reaching maxima at 2-3 weeks. To explore the functional significance of the change, we examined the role of neutral glycosphingolipids as receptors for the murine pulmonary surfactant protein, SP-A, and found that SP-A bound to LacCer, Gg(3)Cer, and Gg(4)Cer, but not to Gb(3)Cer, Gb(4)Cer, IV(3)GalNAc alpha-Gb(4)Cer, sulfatide, or several gangliosides. On TLC-blotting with I-125-labeled SP-A, the binding of SP-A to Gg(3)Cer and Gg(4)Cer was 5 times higher than that to LacCer, and on immunohistochemical staining Gg(3)Cer and Gg(4)Cer was mainly observed in the alveolar epithelium. Thus, the capacity to retain SP-A of glycolipid receptors per gram dry weight of lung at 1 week after birth was 1.6 times higher than that at 1 day after birth, and reached a maximum 3 weeks after birth, These findings suggest that the enhanced synthesis of the ganglio-series neutral glycosphingolipids 1 week after birth results in an increase in the binding capacity for SP-A on the epithelial cell surface of alveoli.