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

Am J Respir Cell Mol Biol. 2005 Jul;33(1):14-21. doi: 10.1165/rcmb.2004-0293OC. Epub 2005 Mar 24.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

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


  • Phospholipids
  • Pulmonary Surfactant-Associated Protein A
  • Pulmonary Surfactant-Associated Protein B
  • Pulmonary Surfactant-Associated Protein C
  • Pulmonary Surfactant-Associated Protein D
  • RNA, Messenger
  • Surface-Active Agents