Chest
Volume 125, Issue 5, May 2004, Pages 1837-1842
Journal home page for Chest

Laboratory and Animal Investigations
Expression of Adhesion Molecules During Apoptosis of Circulating Neutrophils in COPD

https://doi.org/10.1378/chest.125.5.1837Get rights and content

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.

Section snippets

Population and Ethics

Patients with COPD (14 patients) were recruited from the outpatient clinic of our institution. All patients were considered to be clinically stable because none of them had required medical attention and/or a change in their regular therapy (ie, inhaled bronchodilators) during the previous 4 months. None of them had been treated with inhaled or oral corticosteroids. Patients with bronchial asthma, pneumonia, or lung cancer were specifically excluded. Smokers with normal lung function (eight

Clinical Data

Table 1 shows the main clinical and lung function variables of all participants. All of them were men of similar age. The smoking history of patients with COPD was similar to that of smokers with normal lung function. None of the former was a current smoker (Table 1). COPD patients showed moderate-to-severe airflow obstruction and mild-to-moderate hypoxemia (Table 1). By design, the results of forced spirometry were normal in smokers with normal lung function and in healthy nonsmokers (Table 1).

Discussion

This study investigated potential alterations in the process of neutrophil apoptosis in COPD patients that may eventually contribute to the characteristic neutrophil accumulation described in the lungs of these patients.220 The main finding of our study was that, compared to smokers with normal lung function and never-smokers, circulating neutrophils harvested from patients with COPD show similar dynamics of apoptosis in culture, but a differential expression of two adhesion molecules (Mac-1

Conclusions

We found that, quantitatively, the rate of neutrophil apoptosis in vitro is not abnormal in COPD patients compared to healthy smokers or never-smokers. However, our study has identified qualitative differences in the surface expression of several adhesion molecules during the apoptotic process that can contribute to the perpetuation of the inflammatory state that characterizes COPD. The precise relevance of these observations in vivo requires further studies aimed at investigating neutrophil

ACKNOWLEDGMENT

The authors thank C. Erasmo and M. Bosch, for their technical collaboration during the study, and Dr. A. De la Peña (Unidad de Investigación) for his help with the statistical analysis.

References (28)

  • TEJ Renkema et al.

    Influence ofin vivoprednisolone on increasedin vitroO2generation by neutrophils in emphysema

    Eur J Respir Dis

    (1993)
  • C Haslett

    Resolution of acute inflammation and the role of apoptosis in the tissue fate of granulocytes

    Clin Sci

    (1992)
  • G Cox et al.

    Bronchial epithelial cell-derived cytokines (G-CSF and GM-CSF) promote the survival of peripheral blood neutrophils

    Am J Respir Cell Mol Biol

    (1992)
  • PJ Daffern et al.

    Multiple epithelial cell-derived factors enhance neutrophil survival: regulation by glucocorticoids and tumor necrosis factor-alpha

    Am J Respir Crit Care Med

    (1999)
  • Cited by (0)

    Supported, in part, by Sociedad Española de Neumología y Cirucía Torácica, Associació Balear per L'estudi de las Malaltios Respiratorios. Red Respira (RTIC 0311, Fondo de Investigacioues Sanitarias, Instituto de Sahid Carlos III), and Fondo de Investigaciones Sanitarias grant No. 01/0830.

    View full text