ELECTROLYTE COMPOSITION OF SURFACE FLUID IN NORMAL AND CF AIRWAY EPITHELIA

University Of Iowa, Iowa City IA

Investigators

Linked publications & trials

Abstract

(Adapted from the applicant's abstract) The investigators recently proposed a hypothesis to link the molecular and physiologic defect in CF, loss of CFTR C1- channel function and defective transepithelial C1- transport, with the clinical hallmark of CF, airway infections. They and others found that both normal and CF airway epithelia secrete antibacterial substances into the thin layer of fluid covering the apical surface. However the killing activity of these factors require a low NaC1 concentration. Reports that CF surface fluid has a high NaC1 concentration would explain the lack of bacterial killing in CF. They will test three hypotheses about the electrolyte composition of airway surface fluid. First, the salt concentration of airway surface fluid is increased in CF. To test this hypothesis investigators will use primary cultures of normal and CF airway epithelia to measure ion concentrations of ASF, as well as in vivo measurements done in animals and humans. Second, the increase in ASF salt concentration in CF is due to impaired electrolyte absorption. They will test the hypothesis by asking how normal and CF epithelia modify the electrolyte composition of ASF. Third, interventions that decrease salt concentration will restore bactericidal activity. To test this hypothesis they will restore CFTR function by gene transfer, activate alternative (non-CFTR) C1 channels and block epithelial Na+ channels. Investigators will also attempt to use novel approaches to decrease the concentration of salt in ASF. Given its importance, it is surprising that the composition of ASF is not better understood. The studies proposed should provide new insight into the electrolyte concentration of ASF and how they are modified. The results are central to understanding how the lack of CFTR C1- channels causes CF lung disease and to develop new therapies.