title: Altered lung surfactant system in a Rab38-deficient rat model of Hermansky-Pudlak syndrome.
abstract: 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.
authors.affiliation: Dept. of Respiratory Medicine, Kanazawa Medical Univ., 1-1 Uchinada-Daigaku, Kahokugun, Ishikawa 920-0293, Japan. k-osanai@kanazawa-med.ac.jp
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Osanai
authors.forename: Junko
authors.initials: J
authors.lastname: Higuchi
authors.forename: Rieko
authors.initials: R
authors.lastname: Oikawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Katsuma
authors.initials: K
authors.lastname: Tsuchihara
authors.forename: Masaharu
authors.initials: M
authors.lastname: Iguchi
authors.forename: Jyongsu
authors.initials: J
authors.lastname: Huang
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Voelker
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Toga
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D022861:Hermanski-Pudlak Syndrome / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D008081:Liposomes / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D010641:Phenotype; D011663:Pulmonary Surfactants / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020332:Rats, Inbred LEC; D017207:Rats, Sprague-Dawley; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D008081:Liposomes; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; C498787:Rab38 protein, rat; D020691:rab GTP-Binding Proteins