Published ahead of print on March 24, 2005, doi:10.1165/rcmb.2004-0293OC Am. J. Respir. Cell Mol. Biol., Volume 33, Number 1, July 2005, 14-21 A more recent version of this article appeared on July 1, 2005
Submitted on September 15, 2004 Defective Surfactant Secretion in a Mouse Model of Hermansky-Pudlak SyndromeSusan H Guttentag1*,1 Division of Neonatology Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA, 2 Institute for Environmental Medicine and Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA, 3 Pulmonary and Critical Care Division, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA, 4 Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY, USA * To whom correspondence should be addressed. E-mail: guttentag{at}email.chop.edu.
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 SP-B and -C were increased in adult ep/pe mice compared to 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 -C with no differences in SP-A and -D compared to WT. Although LA from ep/pe animals exhibited an increased total protein to total phospholipid ratio compared to 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.
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