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

Susan H. Guttentag, Amana Akhtar, Jian Qin Tao, Elena Nikolaevna Atochina, Michael E. Rusiniak, Richard T. Swank, Sandra R. Bates

Research output: Contribution to journalArticle

57 Citations (Scopus)

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 ∼ 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.

Original languageEnglish
Pages (from-to)14-21
Number of pages8
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume33
Issue number1
DOIs
Publication statusPublished - Jul 2005
Externally publishedYes

Keywords

  • Alveolar type II cell
  • Hermansky-Pudlak syndrome
  • Lamellar body
  • Secretion
  • Surfactant

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology

Fingerprint Dive into the research topics of 'Defective surfactant secretion in a mouse model of Hermansky-Pudlak syndrome'. Together they form a unique fingerprint.

  • Cite this

    Guttentag, S. H., Akhtar, A., Tao, J. Q., Atochina, E. N., Rusiniak, M. E., Swank, R. T., & Bates, S. R. (2005). Defective surfactant secretion in a mouse model of Hermansky-Pudlak syndrome. American Journal of Respiratory Cell and Molecular Biology, 33(1), 14-21. https://doi.org/10.1165/rcmb.2004-0293OC