title: Lamellar body formation in normal and surfactant protein B-deficient fetal mice.
abstract: Surfactant protein B (SP-B) -/- mice die of lethal respiratory distress syndrome shortly after birth. Alveolar type II epithelial cells in SP-B-deficient mice are characterized by a complete absence of lamellar bodies, the intracellular storage form of pulmonary surfactant, and the presence of inclusions containing numerous small vesicles and electron-dense masses. The present study was undertaken to characterize the formation of these inclusions during fetal lung development and clarify their relationship to lamellar bodies. In wild-type and SP-B +/- mice, small lamellar bodies with loosely organized lamellae and distinct limiting membranes were first detected on day 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 inclusions similar to those previously described in late gestation SP-B -/- mice, 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 lamellar 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 vesicles 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 which the absence of SP-B leads to failure to package surfactant phospholipids into concentric lamellae.
authors.affiliation: Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2370, USA. mildred.stahlman@mcmail.vanderbilt.edu
authors.forename: M T
authors.initials: MT
authors.lastname: Stahlman
authors.forename: M P
authors.initials: MP
authors.lastname: Gray
authors.forename: M W
authors.initials: MW
authors.lastname: Falconieri
authors.forename: J A
authors.initials: JA
authors.lastname: Whitsett
authors.forename: T E
authors.initials: TE
authors.lastname: Weaver
mesh_terms: D000818:Animals; D008168:Lung / Q000196:embryology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D011510:Proteolipids / Q000235:genetics*; D011663:Pulmonary Surfactants / Q000235:genetics*
chemical_list: D011510:Proteolipids; D011663:Pulmonary Surfactants