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Background: Chronic hypoxia causes lung pathology but little is known about how morphologic changes occur or about the progenitor cells of lung remodeling. Since the alveolar region is the first site of environmental challenge, smooth muscle cell (SMC) monolayers derived from close to the alveoli were studied for morphologic patterns. Thus we aimed to deduce any impact of environmental challenge on juxta-alveolar cells and identify phenotypical changes that are suspect precedence to lung pathologies such as cancer.
Methods.: Lung tissues from freshly sacrificed adult sheep that had been kept in high altitude hypoxia for ~4 months were used. The lung tissues were studied for macroscopic signs of pathology. Lung parenchymal explants from ~0.5 – 1.5 mm to the lung edge were cultured for isolation of upper generation SMCs which are closer to the air/blood interphase. The cells were characterized by fluorescence immunohistochemistry using a monoclonal antibody against alpha-smooth muscle actin. The monolayer morphologies of the derived stable cell lines were compared.
Results: We observed that the distal lung parenchyma of the chronically hypoxic sheep yielded six distinct smooth muscle cell morphological varieties: apoptotic, sub-confluent, spindle-form, hill and valley, swirl, and rhomboid monolayers. The control sheep lungs yielded two varieties of smooth muscle cells: swirl and hill-and-valley monolayer formations at confluence. All the cell lines were jointly generated from the terminals of the vascular and bronchiolar trees.
Conclusion: Chronic high altitude hypoxia appears to induce morphological variation in juxta-alveolar smooth muscle cells in the ovine lung.
Keywords: Chronic hypoxia, smooth muscle cells, juxta-alveolar, lung
Abstrait
Contexte: L’Hypoxie chronique provoque une pathologiepulmonaire, mais in en sait peu de la façon don’t les hangements morphologiques se produisent ou des cellules progénitrices de remodelage du poumon. Puisque la région alvéolaire est le premier site de défi environnemental, des cellulesmusculaires lisses (CMLs) monocouches provenant de la region des alvéoles ont été étudiées pour des types morphologiques. Ainsi nous avons cherché à déduire un effet quelconque du défi environnemental sur les cellules juxta-alvéolaires et à identifier les modifications phénotypiques qui sont jugées antérieures aux pathologies pulmonaires telles que le cancer.
Méthodes: Des tissus pulmonaires de moutons adultes fraîchement sacrifiés qui avaient été conservés à haute altitude d’hypoxie pendant 4 mois environ ont été utilisés. Les tissus pulmonaires ont fait l’objet d’études visant à détecter des signes macroscopiques de la pathologie. Les explants du parenchyme pulmonaire de ~ 0,5 - 1,5 mm du bord du poumon ont été cultivées pour isoler les CML haute génération qui sont plus proches de l’interface air / sang. Les cellules étaient caractérisées par une immunohistochimie fluorescence se servant d’un anticorps monoclonal dirigé contre l’actine du muscle lisse alpha. Les morphologies monocouches dérivées des lignes cellulaires stables ont été comparées.
Résultats: Nous avons remarqué que le parenchyme pulmonaire distal du mouton chroniquement hypoxique a produit six variétés différentes de cellules musculaires lisses morphologiques: monocouches apoptotiques, sous-confluentes, fusiformes, collines et vallée, tourbillonnaires, et rhomboïdes. Les poumons du moutons contrôle ont produit deux variétés de cellules musculaires lisses: formations monocouches tourbillonnaires et colline-vallée à confluence. Toutes les lignées cellulaires ont été générées conjointement à partir des bornes des arbres vasculaires et bronchiques.
Conclusion: L’Hypoxie chronique de haute altitude semble induire une variation morphologique dans les cellules musculaires lisses juxta-alvéolaires dans le poumon de l’ovin
Correspondence: Dr Therasa A. John, Department of Pharmacology, Lagos State University College of Medicine, PMB 21266, Ikeja, Lagos, Nigeria. E-mail: theresaadebola@yahoo.com
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