%0 Journal Article
%T Nicotinic Receptor ¦Â2 Determines NK Cell-Dependent Metastasis in a Murine Model of Metastatic Lung Cancer
%A Junwei Hao
%A Fu-Dong Shi
%A Mohammed Abdelwahab
%A Samuel X. Shi
%A Alain Simard
%A Paul Whiteaker
%A Ronald Lukas
%A Qinghua Zhou
%J PLOS ONE
%D 2013
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0057495
%X Cigarette smoke exposure markedly compromises the ability of the immune system to protect against invading pathogens and tumorigenesis. Nicotine is a psychoactive component of tobacco products that acts as does the natural neurotransmitter, acetylcholine, on nicotinic receptors (nAChRs). Here we demonstrate that natural killer (NK) cells strongly express nAChR ¦Â2. Nicotine exposure impairs the ability of NK cells to kill target cells and release cytokines, a process that is largely abrogated by nAChR ¦Â2 deficiency. Further, nicotinic suppression of NF-¦ÊB-induced transcriptional activity in NK cells is dependent on nAChR ¦Â2. This nAChR subtype also plays a large role in the NK cell-mediated control of melanoma lung metastasis, in a murine lung metastasis model exposed to nicotine. Our findings suggest nAChR ¦Â2 as a prominent pathway for nicotine induced impairment of NK cell functions which contributes to the occurrence of smoking-related pathologies.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0057495