Interleukin-16-producing NK cells and T-cells in the blood of tobacco smokers with and without COPD
Authors Andersson A, Malmhäll C, Houltz B, Tengvall S, Sjöstrand M, Qvarfordt I, Lindén A, Bossios A
Received 6 January 2016
Accepted for publication 31 May 2016
Published 15 September 2016 Volume 2016:11(1) Pages 2245—2258
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Gee W Lau
Peer reviewer comments 3
Editor who approved publication: Dr Richard Russell
Anders Andersson,1,* Carina Malmhäll,2,* Birgitta Houltz,1 Sara Tengvall,1 Margareta Sjöstrand,2 Ingemar Qvarfordt,1 Anders Lindén,3 Apostolos Bossios2
1Respiratory Medicine and Allergology, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden; 2Krefting Research Center, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden; 3Unit for Lung and Airway Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
*These authors contributed equally to this work
Background: Long-term exposure to tobacco smoke causes local inflammation in the airways that involves not only innate immune cells, including NK cells, but also adaptive immune cells such as cytotoxic (CD8+) and helper (CD4+) T-cells. We have previously demonstrated that long-term tobacco smoking increases extracellular concentration of the CD4+-recruiting cytokine interleukin (IL)-16 locally in the airways. Here, we hypothesized that tobacco smoking alters IL-16 biology at the systemic level and that this effect involves oxygen free radicals (OFR).
Methods: We quantified extracellular IL-16 protein (ELISA) and intracellular IL-16 in NK cells, T-cells, B-cells, and monocytes (flow cytometry) in blood samples from long-term tobacco smokers with and without chronic obstructive pulmonary disease (COPD) and in never-smokers. NK cells from healthy blood donors were stimulated with water-soluble tobacco smoke components (cigarette smoke extract) with or without an OFR scavenger (glutathione) in vitro and followed by quantification of IL-16 protein.
Results: The extracellular concentrations of IL-16 protein in blood did not display any substantial differences between groups. Notably, intracellular IL-16 protein was detected in all types of blood leukocytes. All long-term smokers displayed a decrease in this IL-16 among NK cells, irrespective of COPD status. Further, both NK and CD4+ T-cell concentrations displayed a negative correlation with pack-years. Moreover, cigarette smoke extract caused release of IL-16 protein from NK cells in vitro, and this was not affected by glutathione, in contrast to the decrease in intracellular IL-16, which was prevented by this drug.
Conclusion: Long-term exposure to tobacco smoke does not markedly alter extracellular concentrations of IL-16 protein in blood. However, it does decrease the intracellular IL-16 concentrations in blood NK cells, the latter effect involving OFR. Thus, long-term tobacco smoking exerts an impact at the systemic level that involves NK cells; innate immune cells that are critical for host defense against viruses and tumors – conditions that are overrepresented among smokers.
Keywords: COPD, interleukin-16, NK cells, CD4+ cells, CD8+ cells, CD69+
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