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Expression of Adhesion Molecules During Apoptosis of Circulating Neutrophils in COPD^*

^* From the Serveis de Analisis Cliniques (Drs. Noguera and Pons), Pneumologia (Drs. Sala and Agustí), and Inmunologia (Dr. Iglesias), Hospital Universitari Son Dureta, Palma de Mallorca, Spain; and ELEGI Laboratories (Dr. MacNee), Royal Infirmary, Edinburgh, Scotland, UK.

Correspondence to: Aina Noguera, MD, Servei Analisis Cliniques, Hospital Universitari Son Dureta, Andrea Doria 55, 07014 Palma Mallorca, Spain; e-mail: anoguera{at}hsd.es

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.

Key Words: chronic bronchitis • emphysema • inflammation • programmed cell death

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