Natural Killer Cells in Obesity: Impaired Function and Increased Susceptibility to the Effects of Cigarette Smoke

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Natural Killer Cells in Obesity: Impaired Function and Increased Susceptibility to the Effects of Cigarette Smoke

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dc.contributor.author Cawood, Tom J.
dc.contributor.author O'Farrelly, Cliona
dc.contributor.author Zimmer, Jacques
dc.contributor.author O'Shea, Donal
dc.contributor.author Lynch, Lydia
dc.date.accessioned 2011-06-09T18:01:05Z
dc.date.issued 2010
dc.identifier.citation O'Shea, Donal, Tom J. Cawood, Cliona O'Farrelly, and Lydia Lynch. 2010. Natural Killer Cells in Obesity: Impaired Function and Increased Susceptibility to the Effects of Cigarette Smoke. PLoS ONE 5(1). en_US
dc.identifier.issn 1932-6203 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:4908668
dc.description.abstract Background: Obese individuals who smoke have a 14 year reduction in life expectancy. Both obesity and smoking are independantly associated with increased risk of malignancy. Natural killer cells (NK) are critical mediators of anti-tumour immunity and are compromised in obese patients and smokers. We examined whether NK cell function was differentially affected by cigarette smoke in obese and lean subjects. Methodology and Principal Findings: Clinical data and blood were collected from 40 severely obese subjects (BMI>40 kg/m2) and 20 lean healthy subjects. NK cell levels and function were assessed using flow cytometry and cytotoxicity assays. The effect of cigarette smoke on NK cell ability to kill K562 tumour cells was assessed in the presence or absence of the adipokines leptin and adiponectin. NK cell levels were significantly decreased in obese subjects compared to lean controls (7.6 vs 16.6%, p = 0.0008). NK function was also significantly compromised in obese patients (30% +/− 13% vs 42% +/−12%, p = 0.04). Cigarette smoke inhibited NK cell ability to kill tumour cell lines (p<0.0001). NK cells from obese subjects were even more susceptible to the inhibitory effects of smoke compared to lean subjects (33% vs 28%, p = 0.01). Cigarette smoke prevented NK cell activation, as well as perforin and interferon-gamma secretion upon tumour challenge. Adiponectin but not leptin partially reversed the effects of smoke on NK cell function in both obese (p = 0.002) and lean controls (p = 0.01). Conclusions/Significance Obese: subjects have impaired NK cell activity that is more susceptible to the detrimental effects of cigarette smoke compared to lean subjects. This may play a role in the increase of cancer and infection seen in this population. Adiponectin is capable of restoring NK cell activity and may have therapeutic potential for immunity in obese subjects and smokers. en_US
dc.language.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.relation.isversionof doi://10.1371/journal.pone.0008660 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2801590/pdf/ en_US
dash.license LAA
dc.subject immunology en_US
dc.subject immune response en_US
dc.subject innate immunity en_US
dc.subject nutrition en_US
dc.subject obesity en_US
dc.title Natural Killer Cells in Obesity: Impaired Function and Increased Susceptibility to the Effects of Cigarette Smoke en_US
dc.type Journal Article en_US
dc.description.version Proof en_US
dc.relation.journal PLoS ONE en_US
dash.depositing.author Lynch, Lydia
dc.date.available 2011-06-09T18:01:05Z
dash.affiliation.other HMS^Medicine- Beth Israel-Deaconess en_US

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