Cyclosporin A (CsA), an inhibitor of protein phosphatase 2B (calcineurin),
has been shown to play a role in exocytosis and neutrophil mobility. Hypero
xia (>95% oxygen for 72 h) causes lung injury and reduces lung compliance.
This model is indicative of deficiencies in surfactant and elicits a vigoro
us immune response leading to further damage. We examined the effects of Cs
A on surfactant-secreting lung alveolar type II cells. CsA enhances ATP-sti
mulated increases in whole cell capacitance in the presence of 2 mM extrace
llular Ca2+. This measurement corresponds with increases in exocytosis. Bec
ause 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 hyperox
ia-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 prot
ective effect against hyperoxia-induced changes in neutrophil infiltration,
capillary congestion, edema, and hyaline membrane formation. Wet lung weig
ht-to-dry lung weight ratios did not show any significant changes after hyp
eroxia or hyperoxia plus CsA (P < 0.05). CsA may be useful to treat patient
s undergoing prolonged high-oxygen therapy and possibly other lung injuries
.