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Altered lung surfactant system in a Rab38-deficient rat model of Hermansky-Pudlak syndrome.

Authors: Osanai, K  Higuchi, J  Oikawa, R  Kobayashi, M  Tsuchihara, K  Iguchi, M  Huang, J  Voelker, DR  Toga, H 
Citation: Osanai K, etal., Am J Physiol Lung Cell Mol Physiol. 2010 Feb;298(2):L243-51. Epub 2009 Nov 6.
Pubmed: (View Article at PubMed) PMID:19897744
DOI: Full-text: DOI:10.1152/ajplung.00242.2009

Several Long-Evans rat substrains carrying the phenotype of oculocutaneous albinism and bleeding diathesis are a rat model of Hermansky-Pudlak syndrome (HPS). The mutation responsible for the phenotype (Ruby) was identified as a point mutation in the initiation codon of Rab38 small GTPase that regulates intracellular vesicle transport. As patients with HPS often develop life-limiting interstitial pneumonia accompanied by abnormal morphology of alveolar type II cells, we investigated lung surfactant system in Long-Evans Cinnamon rats, one strain of the Ruby rats. The lungs showed conspicuous morphology of type II cells containing markedly enlarged lamellar bodies. Surfactant phosphatidylcholine and surfactant protein B were increased in lung tissues and lamellar bodies but not in alveolar lumen. Expression levels of mRNA for surfactant proteins A, B, C, and D were not altered. Isolated type II cells showed aberrant secretory pattern of newly synthesized [(3)H]phosphatidylcholine, i.e., decreased basal secretion and remarkably amplified agonist-induced secretion. [(3)H]phosphatidylcholine synthesis and uptake by type II cells were not altered. Thus Rab38-deficient type II cells appear to carry abnormality in lung surfactant secretion but not in synthesis or uptake. These results suggest that aberrant lung surfactant secretion may be involved in the pathogenesis of interstitial pneumonia in HPS.

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CRRD Object Information
CRRD ID: 2324690
Created: 2010-05-11
Species: All species
Last Modified: 2010-05-11
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.