Calcium-modulated chloride pathways contribute to chloride flux in murine cystic fibrosis-affected macrophages

Shenoy, Ambika; Kopic, Sascha; Murek, Michael; Caputo, Christina; Geibel, John P; Egan, Marie E (2011). Calcium-modulated chloride pathways contribute to chloride flux in murine cystic fibrosis-affected macrophages. Pediatric research, 70(5), pp. 447-52. New York, N.Y.: Nature Publishing Group 10.1203/PDR.0b013e31822f2448

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Cystic fibrosis (CF), a common lethal inherited disorder defined by ion transport abnormalities, chronic infection, and robust inflammation, is the result of mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein, a cAMP-activated chloride (Cl-) channel. Macrophages are reported to have impaired activity in CF. Previous studies suggest that Cl- transport is important for macrophage function; therefore, impaired Cl- secretion may underlie CF macrophage dysfunction. To determine whether alterations in Cl- transport exist in CF macrophages, Cl- efflux was measured using N-[ethoxycarbonylmethyl]- 6-methoxy-quinolinium bromide (MQAE), a fluorescent indicator dye. The contribution of CFTR was assessed by calculating Cl- flux in the presence and absence of cftr(inh)-172. The contribution of calcium (Ca(2+))-modulated Cl- pathways was assessed by examining Cl- flux with varied extracellular Ca(2+) concentrations or after treatment with carbachol or thapsigargin, agents that increase intracellular Ca(2+) levels. Our data demonstrate that CFTR contributed to Cl- efflux only in WT macrophages, while Ca(2+)-mediated pathways contributed to Cl- transport in CF and WT macrophages. Furthermore, CF macrophages demonstrated augmented Cl- efflux with increases in extracellular Ca(2+). Taken together, this suggests that Ca(2+)-mediated Cl- pathways are enhanced in CF macrophages compared with WT macrophages.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurosurgery

UniBE Contributor:

Murek, Michael

ISSN:

0031-3998

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:23

Last Modified:

17 Mar 2015 21:02

Publisher DOI:

10.1203/PDR.0b013e31822f2448

PubMed ID:

21796019

Web of Science ID:

000296121100001

URI:

https://boris.unibe.ch/id/eprint/7948 (FactScience: 213336)

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