Hypoxia but not cigarette smoke modulates VEGF secretion from human T cells

Abstract

Vascular endothelial growth factor (VEGF) is an important mitogen with multiple functions. In the present study we investigated whether T cell secreted VEGF and inflammatory cytokines were modulated by cigarette smoke and by a hypoxic microenvironment.

T cells from peripheral blood of healthy donors were activated under normoxia (21% O₂) or hypoxia (1–2% O₂) with or without exposure to cigarette smoke extract. T cells were also obtained from patients with chronic obstructive pulmonary disease (COPD), a smoking-related disease characterized by accumulation of both CD4+ and CD8+T cells.

Hypoxia stimulated VEGF secretion from activated T cells, whereas the release of IL-4, IL-6, IL-10, IL-13, IFN-γ and tumour necrosis factor were not altered. Cigarette smoke extract did not affect VEGF secretion neither in hypoxia nor in normoxia, whereas the secretion of all cytokines was inhibited by the extract in both conditions. When recombinant VEGF was added the smoke-induced inhibition of the IFN-γ and IL-13 was not observed. Activated T cells from COPD-patients secreted significantly (p < 0.05) more VEGF compared to T cells from healthy individuals.

Our data suggest that both cigarette smoke extract and hypoxia modulate the T cell response. This may be of importance in diseases characterized by T cell accumulation, such as COPD.

Keywords::

• VEGF
• T cells
• COPD
• hypoxia
• cigarette smoke

Acknowledgements

We would like to thank Marghita Dahl, Gunnel de Forest and Helene Blomqvist for technical assistance. We would also like to acknowledge Mahdi Mojallal and Jeroen Frijhoff for giving us assistance with the hypoxic chamber. Finally, we would like to thank Per Näsman for statistical advice. This study was supported by grants from the Swedish Heart Lung Foundation, Swedish Research Council, Torsten och Ragnar Söderberg's Foundations, King Oscar II Jubilee Foundation, Mats Kleberg Foundation the Cancer and Allergy Foundation, Karolinska Institutet, the Stockholm County Council, and Hesselman's Foundation. The study was approved by the Regional Ethical Review Board, Stockholm, Sweden, Informed consent was obtained from each subject.

Declaration of interest: The authors declare that they have no competing interests.