Abstract
BackgroundWe have previously shown that NK (CD56+CD3-) and NKT-like (CD56+CD3+) cells are reduced in both numbers and cytotoxicity in peripheral blood. The aim of the present study was to investigate their numbers and function within induced sputum.MethodsInduced sputum cell numbers and intracellular granzyme B and perforin were analysed by flow cytometry. Immunomagnetically selected CD56+ cells (NK and NKT-like cells) were used in an LDH release assay to determine cytotoxicity.ResultsThe proportion of NK cells and NKT-like cells in smokers with COPD (COPD subjects) was significantly higher (12.7% and 3%, respectively) than in healthy smokers (smokers) (5.7%, p < 0.01; 1%, p < 0.001) and non-smoking healthy subjects (HNS) (4.2%, p < 0.001; 0.8%, p < 0.01). The proportions of NK cells and NKT-like cells expressing both perforin and granzyme B were also significantly higher in COPD subjects compared to smokers and HNS. CD56+ cells from COPD subjects were significantly more cytotoxic (1414 biological lytic activity) than those from smokers (142.5; p < 0.01) and HNS (3.8; p < 0.001) and were inversely correlated to FEV1. (r = -0.75; p = 0.0098).ConclusionWe have shown an increased proportion of NK and NKT-like cells in the induced sputum of COPD subjects and have demonstrated that these cells are significantly more cytotoxic in COPD subjects than smokers and HNS.
Highlights
We have previously shown that NK (CD56+CD3-) and NKT-like (CD56+CD3+) cells are reduced in both numbers and cytotoxicity in peripheral blood
There was no significant difference in smoking history between Chronic obstructive pulmonary disease (COPD) subjects and healthy smokers
Comparison of constituent cells in induced sputum The viability of the cells (% total) in induced sputum did not differ between COPD subjects, smokers and healthy non-smokers (HNS): 83 (75-94), 82 (72-93) and 86 (75-94), respectively
Summary
We have previously shown that NK (CD56+CD3-) and NKT-like (CD56+CD3+) cells are reduced in both numbers and cytotoxicity in peripheral blood. Inflammation of the airways is present in COPD with increased numbers of inflammatory cells from both the innate and adaptive host response, such as macrophages and lymphocytes in the airway wall [3] and neutrophils in the airway lumen [4]. Many of these cells have the potential to cause the damage seen in the airways of patients with COPD, including three main heterogeneous and functionally distinct classes of human killer cells; namely CD8+ T lymphocytes, CD56+CD3- (natural killer; NK) cells and CD56+CD3+ (NKT-like) cells [5]. Killer cells lyze their target cells by two mechanisms: membranolysis, in which secreted molecules, such as perforin and granzymes, form pores in the membrane of target cells [6]; and apoptosis, mediated through the triggering of apoptosis-inducing (Fas-like) surface molecules of the target cell [7]
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