Defective surfactant secretion in a mouse model of Hermansky-Pudlak syndrome.

Guttentag SH, Akhtar A, Tao JQ, Atochina E, Rusiniak ME, Swank RT, Bates SR
Am J Respir Cell Mol Biol. 2005 33 (1): 14-21

PMID: 15790974 · PMCID: PMC2715302 · DOI:10.1165/rcmb.2004-0293OC

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.

MeSH Terms (23)

Animals Blotting, Western Bronchoalveolar Lavage Capillaries Densitometry Disease Models, Animal Hermanski-Pudlak Syndrome Humans Immunoblotting Male Mice Mice, Inbred C57BL Mice, Transgenic Microscopy, Fluorescence Phospholipids Pulmonary Surfactant-Associated Protein A Pulmonary Surfactant-Associated Protein B Pulmonary Surfactant-Associated Protein C Pulmonary Surfactant-Associated Protein D Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger Surface-Active Agents Time Factors

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