Referenced in: none

Automatically associated channels: ClC4 , ClC5

Title: Inhibition of human mast cell proliferation and survival by tamoxifen in association with ion channel modulation.

Authors: S Mark Duffy, Wendy J Lawley, Davinder Kaur, Weidong Yang, Peter Bradding

Journal, date & volume: J. Allergy Clin. Immunol., 2003 Nov , 112, 965-72

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/14610489

Abstract
Human lung mast cells (HLMCs) and the human mast cell line HMC-1 express a strongly outwardly rectifying Cl- current characteristic of that carried by the voltage-dependent Cl- channel ClC-5. A similar but distinct current has been implicated in the control of cell proliferation in astrocytes.In this study, we have examined the effects of the Cl- channel blocker tamoxifen on ion channel activity and cell proliferation in both HMC-1 and HLMCs.We used the whole-cell patch-clamp technique to characterize macroscopic ion currents in mast cells before and after addition of tamoxifen. HMC-1 proliferation was assessed by incorporation of tritiated thymidine, HLMC proliferation was determined by counting cells in long-term culture, and cell viability was assessed by annexin V binding and propidium iodide uptake.In HMC-1, tamoxifen reduced the outward Cl- current at +130 mV by 73% +/- 9% at a concentration of 3 micromol/L and simultaneously opened a novel inwardly rectifying nonselective cation current with a mean inward current of 153 +/- 18 pA at -130 mV. Tamoxifen produced a dose-dependent inhibition of HMC-1 proliferation (90.3% +/- 4.0% inhibition at 30 micromol/L) without altering cell viability. Tamoxifen inhibited the outward ClC-5-like current in HLMCs, did not open an inward current, and produced a dose-dependent inhibition of HLMC proliferation in long-term culture.Tamoxifen inhibits HMC proliferation, possibly through ion channel modulation. This suggests that tamoxifen might be useful in the treatment of mast-cell-mediated diseases, including mastocytosis, asthma, and pulmonary fibrosis.