Expression of adhesion molecules during apoptosis of circulating neutrophils in COPD.

STUDY OBJECTIVES Neutrophil accumulation occurs in the lungs of patients with COPD. This can be due to increased recruitment and/or delayed tissue clearance. Previous studies have described alterations in circulating neutrophils in these patients that can facilitate the former. Dysregulation of neutrophil apoptosis may contribute to the latter. This study investigated the potential abnormalities of the apoptotic process in COPD patients. DESIGN Prospective study. SETTINGS Outpatient clinic in a urban, tertiary hospital. PATIENTS Fourteen stable patients with COPD, 8 smokers with normal lung function, and 8 healthy nonsmoking subjects. MEASUREMENTS AND RESULTS We cultured circulating neutrophils that had been harvested from the study subjects at 2, 6, and 24 h. Apoptosis was assessed using flow cytometry by annexin binding and CD16 expression. The surface expression of the adhesion molecules Mac-1 (CD11b) and L-selectin (CD62L) also was determined by flow cytometry. The percentage of apoptotic neutrophils increased with time similarly in all groups. However, the surface expression of Mac-1 (CD11b) was higher, and that of L-selectin (CD62L) was lower, during apoptosis in the neutrophils of patients with COPD. CONCLUSIONS These results show that, quantitatively, in vitro neutrophil apoptosis in COPD patients occurred at a rate similar to that found in healthy individuals and smokers with normal lung function. Qualitatively, however, the increased surface expression of Mac-1 (CD11b) and the decreased surface expression of L-selectin (CD62L) observed in the apoptotic neutrophils of COPD patients indicate increased activation during the apoptotic process. This may be relevant for the pathogenesis of COPD.

[1]  X. Busquets,et al.  Enhanced neutrophil response in chronic obstructive pulmonary disease , 2001, Thorax.

[2]  R. Pauwels,et al.  Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary. , 2001, American journal of respiratory and critical care medicine.

[3]  G. Fernández,et al.  Fibrinogen Promotes Neutrophil Activation and Delays Apoptosis1 , 2001, The Journal of Immunology.

[4]  M. Saetta Airway inflammation in chronic obstructive pulmonary disease. , 1999, American journal of respiratory and critical care medicine.

[5]  T. Hugli,et al.  Multiple epithelial cell-derived factors enhance neutrophil survival. Regulation by glucocorticoids and tumor necrosis factor-alpha. , 1999, American journal of respiratory cell and molecular biology.

[6]  A. Irvine,et al.  Increased apoptotic peripheral blood neutrophils in systemic lupus erythematosus: relations with disease activity, antibodies to double stranded DNA, and neutropenia , 1999, Annals of the rheumatic diseases.

[7]  T. Cotter,et al.  Circulating granulocyte macrophage colony-stimulating factor in plasma of patients with the systemic inflammatory response syndrome delays neutrophil apoptosis through inhibition of spontaneous reactive oxygen species generation. , 1999, Shock.

[8]  A. Rees,et al.  Previous uptake of apoptotic neutrophils or ligation of integrin receptors downmodulates the ability of macrophages to ingest apoptotic neutrophils. , 1999, Blood.

[9]  X. Busquets,et al.  Expression of adhesion molecules and G proteins in circulating neutrophils in chronic obstructive pulmonary disease. , 1998, American journal of respiratory and critical care medicine.

[10]  P. Jeffery,et al.  Structural and inflammatory changes in COPD: a comparison with asthma. , 1998, Thorax.

[11]  R. Kumashiro,et al.  In vitro study of neutrophil apoptosis in liver cirrhosis. , 1998, Internal medicine.

[12]  J. Marshall,et al.  Neutrophil apoptosis is modulated by endothelial transmigration and adhesion molecule engagement. , 1997, Journal of immunology.

[13]  M. Ginsberg,et al.  Trans-dominant inhibition of integrin function. , 1996, Molecular biology of the cell.

[14]  E. Wouters,et al.  Evidence for a relation between metabolic derangements and increased levels of inflammatory mediators in a subgroup of patients with chronic obstructive pulmonary disease. , 1996, Thorax.

[15]  B. Morgan,et al.  Apoptosis is associated with reduced expression of complement regulatory molecules, adhesion molecules and other receptors on polymorphonuclear leucocytes: functional relevance and role in inflammation. , 1995, Immunology.

[16]  G. Cox,et al.  Macrophage engulfment of apoptotic neutrophils contributes to the resolution of acute pulmonary inflammation in vivo. , 1995, American journal of respiratory cell and molecular biology.

[17]  T. Carlos,et al.  Leukocyte-endothelial adhesion molecules. , 1994, Blood.

[18]  N. Hogg,et al.  Neutrophil apoptosis is associated with a reduction in CD16 (Fc gamma RIII) expression. , 1994, Journal of immunology.

[19]  S. Nagata,et al.  Lethal effect of the anti-Fas antibody in mice , 1993, Nature.

[20]  C. Haslett,et al.  Impairment of function in aging neutrophils is associated with apoptosis. , 1993, Journal of immunology.

[21]  C. Haslett Resolution of acute inflammation and the role of apoptosis in the tissue fate of granulocytes. , 1992, Clinical science.

[22]  M. Jordana,et al.  Bronchial epithelial cell-derived cytokines (G-CSF and GM-CSF) promote the survival of peripheral blood neutrophils in vitro. , 1992, American journal of respiratory cell and molecular biology.

[23]  A. Rees,et al.  Glomerular mesangial cells and inflammatory macrophages ingest neutrophils undergoing apoptosis. , 1992, Kidney international.

[24]  Grupo de Trabajo de la Separ,et al.  Normativa para la práctica de la espirometría forzada , 1989 .

[25]  R. Stockley,et al.  NEUTROPHILS FROM SUBJECTS WITH CHRONIC OBSTRUCTIVE LUNG DISEASE SHOW ENHANCED CHEMOTAXIS AND EXTRACELLULAR PROTEOLYSIS , 1987, The Lancet.