Protein changes in airway cells may help balance lung pH in CF
New research findings shed light on cell biology in cystic fibrosis
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Higher than normal levels of several pH-regulating proteins can be found in the bronchial, or airway, cells of people with cystic fibrosis (CF), according to a new study.
This suggests the body may be compensating for the loss of CFTR function — which helps regulate the movement of salt and water in and out of cells — to maintain tissue pH, or acid-base balance.
At the same time, cells from the nasal cavity did not show those same protein changes, and the pH was lower in people with CF, the data showed. That indicates that findings from cultured nasal cells can’t reliably be used to assess changes that occur deeper in the lungs, according to the team.
The researchers say these findings shed light on cell biology in CF.
The study, “Human Nasal and Bronchial Epithelium in Cystic Fibrosis: Differences in Expression of Airway pH Regulatory Proteins,” was published in the journal Pediatric Pulmonology.
In CF, inherited genetic mutations affect the function of CFTR, a protein that normally helps move chloride and bicarbonate — essential electrolyes, or charged minerals — across cell membranes.
When CFTR is defective or absent, the thin layer of fluid that coats the airways, known as the airway surface liquid (ASL), can become more acidic, meaning it has a lower pH. A more acidic ASL helps create an environment with thicker mucus, slower movement of the tiny hairs (cilia) that clear the airway, and reduced ability to fight infections.
Because CFTR is not the only protein that affects ASL pH, a team led by scientists at Indiana University sought to determine whether other pH-regulating proteins are also altered in people with CF.
Researchers used cells collected from people with, without CF
To that end, the research team cultured nasal and bronchial cells collected from three CF patients and three people without the genetic condition, or other airway diseases, until they formed a mature, ciliated airway lining. The levels of 18 different proteins known to affect pH were then measured.
In CF-derived bronchial cells, nine proteins were detected at higher levels than controls: CA1, CA2, CA12, Hv1, LDHA, LDHD, ATP12A, GSNOR, and NOX4. The pattern in nasal cells was different, with only one protein, NOX2, found at lower levels in CF patients than in controls.
When the team measured the pH of the ASL directly, the pH of nasal cell ASL from patients was significantly lower (more acidic) than that of controls (6.69 vs. 7.63). By comparison, no significant difference in ASL pH from bronchial cells was found between the two groups (7.52 vs. 7.26), according to the team.
The researchers noted that this bronchial finding is consistent with some earlier reports that normal pH can be observed in the ASL of people with CF, particularly as they get older. Additionally, an increase in these proteins in bronchial cells could represent a way to compensate for the loss of normal bicarbonate transport that occurs when CFTR function is impaired, the team noted.
Because the measurements were normalized to a reference protein, beta-actin, the team also assessed whether beta-actin levels themselves differed between groups. While no significant differences were found, the beta-actin levels were described as variable overall, making normalization challenging, the scientists said.
“Several pH regulatory proteins are increased in bronchial cells from CF subjects compared to those from control subjects,” the researchers wrote. “Changes in the expression of pH regulatory proteins may help maintain ASL pH [balance] and thereby regulate airway [surface] function,”
As study limitations warranting further research, the team mentioned the small number of participants and the fact that they did not “evaluate the mechanisms, causes or effects of the differences in pH-regulatory protein expression we observed.”
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