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PubMed · 10330035

Cyclosporin A protects lung function from hyperoxic damage.

E Matthew·R Pun·M Simonich·H Iwamoto·J Dedman
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Abstract

Cyclosporin A (CsA), an inhibitor of protein phosphatase 2B (calcineurin), has been shown to play a role in exocytosis and neutrophil mobility. Hyperoxia (>95% oxygen for 72 h) causes lung injury and reduces lung compliance. This model is indicative of deficiencies in surfactant and elicits a vigorous immune response leading to further damage. We examined the effects of CsA on surfactant-secreting lung alveolar type II cells. CsA enhances ATP-stimulated increases in whole cell capacitance in the presence of 2 mM extracellular Ca2+. This measurement corresponds with increases in exocytosis. Because of its effect on the immune system and exocytosis from type II cells, CsA was examined for its protective effects against hyperoxia-induced lung damage in mice. We found that CsA (50 mg. kg-1. day-1) attenuated hyperoxia-induced reductions in lung compliance when administered before or during 72 h of >95% oxygen (P < 0.05). CsA (10 mg. kg-1. day-1) also had a protective effect against hyperoxia-induced changes in neutrophil infiltration, capillary congestion, edema, and hyaline membrane formation. Wet lung weight-to-dry lung weight ratios did not show any significant changes after hyperoxia or hyperoxia plus CsA (P < 0. 05). CsA may be useful to treat patients undergoing prolonged high-oxygen therapy and possibly other lung injuries.

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Adenosine TriphosphateAnimalsCalcineurin InhibitorsCells, CulturedCyclosporineEnzyme InhibitorsExocytosisFemaleHyperoxiaLungLung ComplianceLung DiseasesMiceNeutrophilsProteolipidsPulmonary AlveoliPulmonary SurfactantsTissue DistributionJournal ArticleResearch Support, U.S. Gov't, P.H.S.

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E Matthew, R Pun, M Simonich, H Iwamoto, J Dedman. 1999. Cyclosporin A protects lung function from hyperoxic damage.. https://doi.org/10.1152/ajplung.1999.276.5.l786

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