Calcium and cystic fibrosis

Cystic fibrosis (CF) is a generally lethal, congenital, genetic disease of unknown etiology. It is likely that a defective regulation of ion and water transport in exocrine glands and possibly also in other epithelial cells has a central role in the pathogenesis of this disease. Calcium has been implicated in the basic defect underlying CF because of findings of abnormally high calcium levels in some secreted fluids and some cells of CF patients. Using X-ray microanalysis, we have demonstrated elevated calcium concentrations in cultured fibroblasts and in goblet cells of the bronchial epithelium of CF patients. A factor produced by CF fibroblasts in culture can increase the calcium concentration in healthy cells, although this may be an indirect effect. In animal models for CF, such as the chronically reserpinized rat and the chronically isoproterenol-treated rat, abnormally high calcium levels in the acinar cells of the submandibular gland could be demonstrated, similar to the situation in CF patients. In the acinar cells of the parotid gland in these animal models, the calcium levels are, however, abnormally low. This suggests that the changes in cell calcium content are secondary to other changes, possibly changes in the secretory proteins. A study of the effect of the serum calcium level and of the calciotropic hormone calcitonin suggested that neither of these factors could be directly linked with CF. It is concluded that several lines of evidence point to a secondary rather than a primary role for calcium in the pathogenesis of CF.