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 language | English |
|---|---|
| Pages (from-to) | 14-21 |
| Number of pages | 8 |
| Journal | American Journal of Respiratory Cell and Molecular Biology |
| Volume | 33 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jul 2005 |
| Externally published | Yes |
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Keywords
- Alveolar type II cell
- Hermansky-Pudlak syndrome
- Lamellar body
- Secretion
- Surfactant
ASJC Scopus subject areas
- Cell Biology
- Pulmonary and Respiratory Medicine
- Molecular Biology
Cite this
Defective surfactant secretion in a mouse model of Hermansky-Pudlak syndrome. / Guttentag, Susan H.; Akhtar, Amana; Tao, Jian Qin; Atochina, Elena Nikolaevna; Rusiniak, Michael E.; Swank, Richard T.; Bates, Sandra R.
In: American Journal of Respiratory Cell and Molecular Biology, Vol. 33, No. 1, 07.2005, p. 14-21.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Defective surfactant secretion in a mouse model of Hermansky-Pudlak syndrome
AU - Guttentag, Susan H.
AU - Akhtar, Amana
AU - Tao, Jian Qin
AU - Atochina, Elena Nikolaevna
AU - Rusiniak, Michael E.
AU - Swank, Richard T.
AU - Bates, Sandra R.
PY - 2005/7
Y1 - 2005/7
N2 - 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.
AB - 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.
KW - Alveolar type II cell
KW - Hermansky-Pudlak syndrome
KW - Lamellar body
KW - Secretion
KW - Surfactant
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UR - http://www.scopus.com/inward/citedby.url?scp=21844441925&partnerID=8YFLogxK
U2 - 10.1165/rcmb.2004-0293OC
DO - 10.1165/rcmb.2004-0293OC
M3 - Article
VL - 33
SP - 14
EP - 21
JO - American Journal of Respiratory Cell and Molecular Biology
JF - American Journal of Respiratory Cell and Molecular Biology
SN - 1044-1549
IS - 1
ER -