Abstract
Recent reports suggest an important role for pulmonary surfactant in maintaining the patency of narrow conducting airways. The hypothesis that surfactant dysfunction is an important factor in respiratory syncytial virus(RSV) infection was tested in a mouse model. Mice, inoculated with either a low or a high dose of RSV, were subjected to bronchoalveolar lavage (BAL), and the fluids were analyzed for percentage of inflammatory cells and concentrations of proteins and phospholipids. After concentration of the surfactant by centrifugation, its function was analyzed with a capillary surfactometer. RSV infection resulted in a dose-dependent disruption of surfactant function (p < 0.0001). BAL fluid supernatants were added to calf lung surfactant extract (CLSE) to examine whether surfactant inhibiting agents were present. Indeed, BAL fluid supernatants of RSV-infected mice disrupted the normal function of calf lung surfactant extract in a dose dependent way (p < 0.0001), indicating the presence of inhibitors. Protein concentrations were increased in BAL fluids of RSV-infected mice versus control mice (p < 0.0001), and were inversely related to surfactant function (r = -0.44,p = 0.0004), suggesting an inhibitory effect of proteins. Protein concentration also correlated with the percentage of inflammatory cells(r = 0.51, p = 0.004). Phospholipid concentrations were not affected by the RSV infection. The results of these studies strongly suggest that a disruption of pulmonary surfactant function, most likely due to inhibition from inflammatory proteins, is important for the pathophysiology of RSV infection.
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Abbreviations
- BAL:
-
bronchoalveolar lavage
- CLSE:
-
calf lung surfactant extract
- pfu:
-
plaque-forming unit
- RSV:
-
respiratory syncytial virus
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Acknowledgements
The authors thank Dr. L. C. Duffy for her advice on statistical analyses.
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Supported by The Kettering Family Foundation and Grant HL49971 from the National Heart, Lung and Blood Institute of the National Institutes of Health.
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Van Schaik, S., Vargas, I., Welliver, R. et al. Surfactant Dysfunction Develops in BALB/c Mice Infected with Respiratory Syncytial Virus. Pediatr Res 42, 169–173 (1997). https://doi.org/10.1203/00006450-199708000-00007
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DOI: https://doi.org/10.1203/00006450-199708000-00007
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