Changes of peripheral blood lymphocyte and leukocyte functions in Chronic Obstructive Pulmonary Disease

Introduction: Chronic obstructive pulmonary disease (COPD) is characterized by a chronic progressive inflammatory process predominantly in the small airways and lung parenchyma, with increased numbers of macrophages, neutrophils, and lymphocytes. The role of lymphocyte apoptosis as an important factor in regulation of systemic immune response in COPD patients is not yet certain.

Methods: We studied 125 patients with COPD (stage I-IV) during acute exacerbation. The age range was 25 to 86 years. COPD was diagnosed according to the criteria recommended by the Global Initiative of Obstructive Lung Disease (GOLD, 2003). Blood samples of patients were collected after obtaining informed consent. All assays were conducted in vitro. Phagocytic activity of monocytes and neutrophils was investigated by latex bead ingestion method. T-cell surface antigens were studied by indirect immunofluorescence microscopy (IEF) using monoclonal antibodies against CD3, CD4, CD8, CD16, CD95 («Sorbent», Moscow). Apoptotic lymphocytes were quantified from blood samples stained with acridine orange and ethidium bromide in phosphate buffer.

Results: Significant reduction of monocytes' and neutrophils' phagocytic activity was observed in the case of severe forms of COPD (stage III and IV). At all stages of the disease, the percentage of CD-lymphocytes (CD3, CD4, CD8, CD16) in blood was a significantly lower than in the control (healthy) group. Particularly, a decrease in T-cell subpopulations (CD4+, CD8+) was observed in COPD stages III and IV. The percentage of T-cells positive for CD95, necessary for Fas-dependent apoptosis, was decreased at all stages of COPD compared with controls. An accumulation of apoptotic cells in peripheral blood was revealed in COPD stage II-IV.

Discussion: Our data suggest that apoptotic cells accumulate in the systemic circulation in COPD stage II-IV, which suggest that mechanisms to remove defective cells from the blood are disturbed. The increase in apoptotic lymphocytes in the systemic circulation was combined with a reduction of the phagocytic activity of monocytes and neutrophils.