Natural killer cells in obesity: impaired function and increased susceptibility to the effects of cigarette smoke.

Hdl Handle:
http://hdl.handle.net/10147/93876
Title:
Natural killer cells in obesity: impaired function and increased susceptibility to the effects of cigarette smoke.
Authors:
O'Shea, Donal; Cawood, Tom J; O'Farrelly, Cliona; Lynch, Lydia
Affiliation:
Department of Endocrinology, St. Vincent's University Hospital, Dublin, Ireland.
Citation:
Natural killer cells in obesity: impaired function and increased susceptibility to the effects of cigarette smoke. 2010, 5 (1):e8660 PLoS ONE
Journal:
PloS one
Issue Date:
2010
URI:
http://hdl.handle.net/10147/93876
DOI:
10.1371/journal.pone.0008660
PubMed ID:
20107494
Abstract:
BACKGROUND: Obese individuals who smoke have a 14 year reduction in life expectancy. Both obesity and smoking are independently 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/m(2)) 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.
Language:
en
ISSN:
1932-6203

Full metadata record

DC FieldValue Language
dc.contributor.authorO'Shea, Donalen
dc.contributor.authorCawood, Tom Jen
dc.contributor.authorO'Farrelly, Clionaen
dc.contributor.authorLynch, Lydiaen
dc.date.accessioned2010-03-08T14:44:23Z-
dc.date.available2010-03-08T14:44:23Z-
dc.date.issued2010-
dc.identifier.citationNatural killer cells in obesity: impaired function and increased susceptibility to the effects of cigarette smoke. 2010, 5 (1):e8660 PLoS ONEen
dc.identifier.issn1932-6203-
dc.identifier.pmid20107494-
dc.identifier.doi10.1371/journal.pone.0008660-
dc.identifier.urihttp://hdl.handle.net/10147/93876-
dc.description.abstractBACKGROUND: Obese individuals who smoke have a 14 year reduction in life expectancy. Both obesity and smoking are independently 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/m(2)) 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.-
dc.language.isoenen
dc.titleNatural killer cells in obesity: impaired function and increased susceptibility to the effects of cigarette smoke.en
dc.contributor.departmentDepartment of Endocrinology, St. Vincent's University Hospital, Dublin, Ireland.en
dc.identifier.journalPloS oneen
dc.description.provinceLeinster-

Related articles on PubMed

All Items in Lenus, The Irish Health Repository are protected by copyright, with all rights reserved, unless otherwise indicated.