Increased peripheral blood T-cell apoptosis and decreased Bcl-2 in chronic obstructive pulmonary disease.
Chronic obstructive pulmonary disease (COPD) is an inflammatory airway disease, usually associated with cigarette smoking. Stimulated peripheral blood T cells from patients with COPD have an increased propensity to undergo apoptosis. The mitochondrial apoptotic pathway is regulated by pro-apoptotic proteins (including p53 and Bax) as well as anti-apoptotic proteins (e.g. Bcl-2) and cytokines (IL-2, IL-4 and IL-7). We hypothesized that alterations in expression of these apoptosis-related proteins, cytokines and cytokine receptors may be important in determining the susceptibility of T cells to undergoing apoptosis in COPD. We further hypothesized that inhaled corticosteroids (GCS) contribute to the increased rates of T-cell apoptosis observed in COPD. The process of apoptosis (assessed by Annexin V and ssDNA staining), as well as Bcl-2, Bax, p53, IL-2, IL-4 and receptors IL-7R, IL-4R and IL-2Rgamma were investigated in PHA-stimulated peripheral blood-derived T cells, using flow cytometry. Fifteen patients with COPD receiving inhaled GCS (four of who received additional prednisolone), eight patients with COPD receiving symptom control medication, and 16 control subjects were studied. T cells (CD4(+) and CD8(+)) from GCS-treated COPD patients showed an increased propensity to undergo apoptosis, associated with significantly decreased Bcl-2 and IL-7 receptor expression. No significant differences were observed for the COPD patients who were receiving symptom control medication. These findings may suggest a negative peripheral effect of inhaled GCS on the immune system in COPD, although the clinical significance of these effects remains uncertain.
Hodge
Sandra
S
Department of Thoracic Medicine, Royal Adelaide Hospital and Lung Research Laboratory, Hanson Institute, Adelaide, South Australia, Australia. sandy.hodge@imvs.sa.gov.au
Hodge
Greg
G
Holmes
Mark
M
Reynolds
Paul N
PN
D000368:Aged; D017209:Apoptosis / Q000276:immunology / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology / Q000378:metabolism*; D018121:Receptors, Cytokine / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D016207:Cytokines; D019253:Proto-Oncogene Proteins c-bcl-2; D018121:Receptors, Cytokine; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein