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Newly Discovered Immune Defense May Be Impaired In CF Airways

A recent University of Iowa study reveals a new immune defense mechanism in normal airways and may help explain why people// with cystic fibrosis (CF) are particularly susceptible to bacterial lung infections. The findings also may point the way to new approaches for treating the disease.

The UI study shows how two enzymes generate and use reactive oxygen species (ROS) to destroy bacteria in normal airways. The team also found that this process is defective in airway tissue and cells containing the CF gene mutation. The study is published in the Nov. 2 online issue of the American Journal of Respiratory and Critical Care Medicine.

"Among the host defense systems that we know of in the airway, at least in cell culture and tissue explants, this is one of the most efficient antibacterial system we have identified," said Botond Banfi, M.D., Ph.D., UI assistant professor of anatomy and cell biology and senior study author. "The findings suggest that one reason for CF patients' weakened innate immunity might be the absence of this natural oxidative host defense mechanism."

Banfi added that correcting the problem by reconstituting the oxidative system might represent a totally new approach for preventing the onset of bacterial lung infections that often become chronic and eventually fatal in CF patients.

Working with airway cells and tissues from rats, cows and humans, the UI team uncovered the oxidative system, which produces hypothiocyanite -- a highly effective antibacterial compound. Banfi and his colleagues, including Patryk Moskwa, M.D., Ph.D., a UI postdoctoral fellow and first author of the study, showed that one airway enzyme (Duox) makes hydrogen peroxide and a second enzyme (lactoperoxidase) uses the hydrogen peroxide to convert a small molecule called thiocyanate into the bacteria-killing hypothiocyanite.

The UI researchers also showed that the critical thiocyanate cannot be transported across airway c
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