Activated T-Lymphocytes and Macrophages in Bronchial Mucosa of Subjects with Chronic Bronchitis

Abstract

To examine the nature and the degree of leukocyte infiltration and to determine the state of activation of cells in bronchial mucosa of subjects with chronic bronchitis, bronchoscopy was performed in 10 subjects with a history of cigarette smoking and chronic sputum production and in six normal nonsmoking control subjects. Lobar bronchial biopsies were examined using histochemical and immunohistochemical techniques. Subjects with chronic bronchitis had an increased number of total leukocytes (CD45 positive cells), both in the epithelium and in the lamina propria, than did the control subjects (p < 0.05), whereas the numbers of neutrophils, eosinophils, and mast cells were similar in the two groups. There was a significant increase in the numbers of macrophages (p < 0.01) and of T-lymphocytes (CD3 positive cells) (p < 0.05) in the lamina propria of chronic bronchitics, whereas the relative proportions of CD4 and CD8 positive cells were similar in the bronchitics and the control subjects. Subjects with chronic bronchitis also had an increased expression of markers of lymphocyte activation, i.e., an increased number of interleukin-2 receptor positive cells (CD25 positive cells) (p < 0.05) and an increased number of very late activation antigen (VLA-1) positive cells (p < 0.05). In conclusion, the present study provides evidence for mononuclear cell infiltration and for T-cell activation in bronchial mucosa of subjects with chronic bronchitis, supporting the involvement of these cells in the pathogenesis of the disease.

Subepithelial immunopathology of the large airways in smokers with and without chronic obstructive pulmonary disease

“…The absence of any correlation between the number of neutrophils infiltrating the large airway subepithelium and increasing obstruction is consistent with previous studies which have reported no increase in neutrophils in the large [4,5,8,11] or the small airways [15,24] in subjects with COPD. The discordance of these results with those showing an increase in numbers of neutrophils and markers of neutrophil activation in bronchoalveolar lavage [10,11,13,14,25], induced sputum [26±28] and airway epithelium [29] remains to be explained.…”

“…Previous studies have demonstrated an increase in the number of T-cells infiltrating the large airway subepithelium and a shift towards a CD8 phenotype [3±8] in addition to increases in the number of macrophages [4,5,8]. An increase in the number of infiltrating eosinophils has been observed in the large airway subepithelium although they do not appear to be degranulated as in asthma [9].…”

“…An increase in the number of infiltrating eosinophils has been observed in the large airway subepithelium although they do not appear to be degranulated as in asthma [9]. Although studies examining bronchoalveolar lavage have demonstrated increases in the number of neutrophils in subjects with COPD [10±14] this has not been supported by the majority of studies of the large airway subepithelium [4,5,8,11].…”

Release of transforming growth factor-beta (TGF-β) and fibronectin by alveolar macrophages in airway diseases

“…In chronic bronchitis, airway wall fibrosis has also been demonstrated [32,33]. The elevated levels of TGF-and FN released by AM from patients with chronic bronchitis may be of importance in the regulation of fibrosis, since airways macrophages are increased in numbers in the bronchial mucosa [13].…”

Interleukin-18 production and pulmonary function in COPD

“…Increased numbers of CD8+ T-cells, alveolar macrophages and neutrophils are characteristic pathological features of the lungs in COPD [3,4]. Eosinophil numbers are increased during exacerbations and possibly also during stable phases in a subset of patients [5].…”