title: Defective surfactant secretion in a mouse model of Hermansky-Pudlak syndrome.
abstract: Hermansky-Pudlak syndrome (HPS) in humans represents a family of disorders of lysosome-related organelle biogenesis associated with severe, progressive pulmonary disease. Human case reports and a mouse model of HPS, the pale ear/pearl mouse (ep/pe), exhibit giant lamellar bodies (GLB) in type II alveolar epithelial cells. We examined surfactant proteins and phospholipid from ep/pe mice to elucidate the process of GLB formation. The 2.8-fold enrichment of tissue phospholipids in ep/pe mice resulted from accumulation from birth through adulthood. Tissue surfactant protein (SP)-B and -C were increased in adult ep/pe mice compared with wild-type mice (WT), whereas SP-A and -D were not different. Large aggregate surfactant (LA) from adult ep/pe mice had decreased phospholipid, SP-B, and SP-C, with no differences in SP-A and -D compared with WT. Although LA from ep/pe animals exhibited an increased total protein-to-total phospholipid ratio compared with WT, surface tension was not compromised. Phospholipid secretion from isolated type II cells showed that basal and stimulated secretion from ep/pe cells were approximately 50% of WT cells. Together, our data indicate that GLB formation is not associated with abnormal trafficking or recycling of surfactant material. Instead, impaired secretion is an important component of GLB formation in ep/pe mice.
authors.affiliation: Division of Neonatology, Department of Pediatrics, Children's Hospital of Philadelphia, 19104-4318, USA. guttentag@email.chop.edu
authors.forename: Susan H
authors.initials: SH
authors.lastname: Guttentag
authors.forename: Amana
authors.initials: A
authors.lastname: Akhtar
authors.forename: Jian-Qin
authors.initials: JQ
authors.lastname: Tao
authors.forename: Elena
authors.initials: E
authors.lastname: Atochina
authors.forename: Michael E
authors.initials: ME
authors.lastname: Rusiniak
authors.forename: Richard T
authors.initials: RT
authors.lastname: Swank
authors.forename: Sandra R
authors.initials: SR
authors.lastname: Bates
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018893:Bronchoalveolar Lavage; D002196:Capillaries / Q000378:metabolism; D003720:Densitometry; D004195:Disease Models, Animal; D022861:Hermanski-Pudlak Syndrome / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D015151:Immunoblotting; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D010743:Phospholipids / Q000378:metabolism; D037662:Pulmonary Surfactant-Associated Protein A / Q000096:biosynthesis; D037701:Pulmonary Surfactant-Associated Protein B / Q000096:biosynthesis; D037721:Pulmonary Surfactant-Associated Protein C / Q000096:biosynthesis; D037663:Pulmonary Surfactant-Associated Protein D / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013501:Surface-Active Agents / Q000378:metabolism*; D013997:Time Factors
chemical_list: D010743:Phospholipids; D037662:Pulmonary Surfactant-Associated Protein A; D037701:Pulmonary Surfactant-Associated Protein B; D037721:Pulmonary Surfactant-Associated Protein C; D037663:Pulmonary Surfactant-Associated Protein D; D012333:RNA, Messenger; D013501:Surface-Active Agents