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Normalizing pH in lungs of CF patients may prevent chronic infections

מתוך medicontex.co.il

WESTPORT, CT (Reuters Health) – A dysfunctional gene in patients with cystic fibrosis (CF) results in excess acid production in lung cells, investigators report in the Proceedings of the National Academy of Sciences early online edition for November 20. Neutralizing this acid appears to reduce the numbers of bacteria that colonize the respiratory tract.

Dr. Vojo Deretic, of the University of New Mexico School of Medicine in Albuquerque, and associates worked with cells from a human bronchial epithelial cell line derived from a patient with CF who had a CF transmembrane conductance regulator (CFTR) mutant genotype.

The trans-Golgi network in these cells was more acidic than in CFTR-corrected cells, with mean pH of 6.3 and 6.7, respectively. One result of this hyperacidification, the investigators found, was undersialylation of glycoconjugates on CF cells.

Incubation of the CFTR-mutant cells with low concentrations of ammonium chloride or chloroquine corrected the pH. Furthermore, patterns of lectin binding were restored to normal by alkalization of the cells.

Previous studies have shown that Pseudomonas aeruginosa preferentially binds to undersialylated glycoconjugates, the researchers note. They found that P. aeruginosa was significantly less likely to adhere to the ammonia-treated cells than to untreated cells.

"The correction of the undersialylation defect and bacterial adherence by using low concentrations of weak bases has strong therapeutic implications as pH-normalizing drugs may prove beneficial in the treatment of CF," Dr. Deretic and his associates conclude.

"We already have ion pump inhibitors and antacids for treating heartburn," Dr. Deretic stated in a news release from the National Institute of Allergy and Infectious Diseases. "If we can design similar compounds to go to the lungs, we might have a simple solution to greatly improve the health of CF patients."

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