Lamellar body formation in normal and surfactant protein B-deficient fetalmice

Surfactant protein B (SP-B) -/- mice die of lethal respiratory distress syn drome shortly after birth. Alveolar type II epithelial cells in SP-B-defici ent mice are characterized by a complete absence of lamellar bodies, the in tracellular storage form of pulmonary surfactant, and the presence of inclu sions containing numerous small vesicles and electron-dense masses. The pre sent study was undertaken to characterize the formation of these inclusions during fetal lung development and clarify their relationship to lamellar b odies. In wild-type and SP-B +/- mice, small lamellar bodies with loosely o rganized lamellae and distinct limiting membranes were first detected on da y 16 to 16.5 of gestation. SP-B -/- mice were readily identified on day 16 by the absence of immature lamellar bodies, the appearance of vesicular inc lusions similar to those previously described in late gestation SP-B -/- mi ce, and the accumulation of misprocessed SP-C protein. Vesicular inclusions were rarely detected in SP-B +/- mice and were never detected in wild-type littermates. Classical multivesicular bodies were observed fusing with lam ellar bodies in wild-type mice, and with the vesicular inclusions in SP-B - /- mice that occasionally contained a few membrane lamellae. On day 18, the airways of SP-B -/- mice lacked tubular myelin and were filled with vesicl es and electron-dense masses, suggesting that the contents of the vesicular inclusions were secreted. Taken together, these observations suggest that vesicular inclusions in SP-B -/- mice are disorganized lamellar bodies in w hich the absence of SP-B leads to failure to package surfactant phospholipi ds into concentric lamellae.