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

Hdl Handle:
http://hdl.handle.net/10147/207504
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:
PLoS One. 2010 Jan 25;5(1):e8660.
Journal:
PloS one
Issue Date:
1-Feb-2012
URI:
http://hdl.handle.net/10147/207504
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:
eng
MeSH:
Adipokines/physiology; Cytokines/biosynthesis; Female; Flow Cytometry; Humans; Killer Cells, Natural/*immunology; Male; Obesity/*immunology; *Smoke; *Tobacco
ISSN:
1932-6203 (Electronic); 1932-6203 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorO'Shea, Donalen_GB
dc.contributor.authorCawood, Tom Jen_GB
dc.contributor.authorO'Farrelly, Clionaen_GB
dc.contributor.authorLynch, Lydiaen_GB
dc.date.accessioned2012-02-01T10:29:42Z-
dc.date.available2012-02-01T10:29:42Z-
dc.date.issued2012-02-01T10:29:42Z-
dc.identifier.citationPLoS One. 2010 Jan 25;5(1):e8660.en_GB
dc.identifier.issn1932-6203 (Electronic)en_GB
dc.identifier.issn1932-6203 (Linking)en_GB
dc.identifier.pmid20107494en_GB
dc.identifier.doi10.1371/journal.pone.0008660en_GB
dc.identifier.urihttp://hdl.handle.net/10147/207504-
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.en_GB
dc.language.isoengen_GB
dc.subject.meshAdipokines/physiologyen_GB
dc.subject.meshCytokines/biosynthesisen_GB
dc.subject.meshFemaleen_GB
dc.subject.meshFlow Cytometryen_GB
dc.subject.meshHumansen_GB
dc.subject.meshKiller Cells, Natural/*immunologyen_GB
dc.subject.meshMaleen_GB
dc.subject.meshObesity/*immunologyen_GB
dc.subject.mesh*Smokeen_GB
dc.subject.mesh*Tobaccoen_GB
dc.titleNatural killer cells in obesity: impaired function and increased susceptibility to the effects of cigarette smoke.en_GB
dc.contributor.departmentDepartment of Endocrinology, St. Vincent's University Hospital, Dublin, Ireland.en_GB
dc.identifier.journalPloS oneen_GB
dc.description.provinceLeinster-

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