Natural killer cells in obesity: impaired function and increased susceptibility to the effects of cigarette smoke.
Citation:
O'Shea, D., Cawood, T.J., O'Farrelly, C., Lynch, L., Natural killer cells in obesity: impaired function and increased susceptibility to the effects of cigarette smoke., PloS one, 5, 1, 2010, e8660Download Item:
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/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%
+
/
2
13% vs 42%
+
/
2
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
Sponsor
Grant Number
Health Research Board (HRB)
Author's Homepage:
http://people.tcd.ie/ofarreclhttp://people.tcd.ie/lynchl3
Description:
PUBLISHEDPubMed ID: 20107494
Author: O'FARRELLY, CLIONA; LYNCH, LYDIA
Type of material:
Journal ArticleCollections
Series/Report no:
PloS one5
1
Availability:
Full text availableKeywords:
AdiponectinSubject (TCD):
Immunology, Inflammation & InfectionDOI:
http://dx.doi.org/10.1371/journal.pone.0008660Metadata
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