Lymphocytes Apoptosis in Patients with Acute Exacerbation of Asthma

Abstract

Asthma is characterized by airway inflammation, which can be now assessed by the analysis of induced sputum. Ten patients with asthma were investigated during acute exacerbation for the quantification of apoptosis, for Bcl-2 and Fas expression, in induced sputum lymphocytes. They were compared to 12 patients with chronic obstructive pulmonary disease (COPD), and 10 healthy controls. Spontaneous apoptosis was determined by staining nuclei with propidium iodide, and analyzed with a FACScan. Bcl-2 was measured by Western blotting, and results were obtained by densitometric scanning, done by the gel proanalyser. The investigation of Fas was performed using the streptavidin-biotin preroxidase-complex method. Patients with asthma and patients with COPD exhibited a significant increase of cellularity, percentage of neutrophils, eosinophils and lymphocytes when compared to healthy controls. Apoptosis in induced sputum mononuclear cells was found decreased in patients with asthma compared to COPD patients and healthy controls. The quantification of apoptosis was measured after exposure to anti-cytokine antibodies. Anti-TNF-alpha antibody blocked the apoptosis in both patients groups and healthy controls, suggesting that TNF-alpha acted as an inducer of apoptosis. Anti-IL-10 blocked apoptosis completely exclusively in patients with asthma. Bcl-2 expression was found to be increased in induced sputum mononuclear cells from patients with asthma, compared to healthy controls and patients with COPD. Expression of Fas could be detected in patients with asthma, at a lower level than COPD patients and healthy controls. Distinct mechanisms of apoptosis were found in patients with asthma and patients with COPD, characterized by different levels of Bcl-2 and Fas expression. Induction of apoptosis should be a beneficial process in allergic inflammation traduced in induced sputum mononuclear cells. The apoptosis process is assumed by two different mechanisms in asthma and COPD. Our findings indicated that in asthmatic patients, activated lymphocytes accumulate in the bronchi; because of their prolonged survival that maintains inflammation.

Lymphocytes sensitivity to Fas stimulation in healthy and asthmatic children.

“…Similar observation was confirmed by Hanzaoui et al They analysed the percentage of apoptotic cells in sputum from asthmatic subjects. These authors discovered that the percentage of apoptotic lymphocytes in sputum from asthmatics is lower than in healthy or COPD patients [1]. Our results are in the line with these observations.…”

“…The CD4+ T lymphocytes play a major role in the pathogenesis of asthma. They regulate recruitment and activation of airway eosinophils and IgE production [1].…”

Cyclosporin A, apoptosis of BAL T-cells and expression of Bcl-2 inasthmatics

“…Although apoptosis may provide a mechanism for the removal of activated T-cells in health, recent studies have suggested that this process may be delayed in the airways of asthmatics [14][15][16][17][18]. For example, apoptosis of lymphocytes was decreased at baseline in asthmatics compared to normal controls and patients with chronic obstructive pulmonary disease (COPD) [14].…”

Peningkatan Ekspresi Interleukin (IL)-4 Berhubungan dengan Penurunan Bax dan Apoptosis Limfosit pada Bronkiolus dan Paru Mencit Asma

“…Fas dibandingkan dengan subyek normal (32 pemeriksaan secara serial mulai dari paparan awal Untuk menganalisis kekuatan peran peningkatan sampai dengan paparan akhir (paparan kronis), (2) ekspresi IL-4 dan penurunan ekspresi Bax limfosit pemeriksaan petanda (marker) limfosit untuk terhadap penurunan apoptosis limfosit, serta jalur menentukan subset limfosit (terutama sel T CD4+), yang lebih berperan, dilakukan analisis jalur (path (3) pemeriksaan dengan teknik flow cytometry analysis) (38). Berdasarkan analisis jalur, peran karena dapat diukur ekspresi IL-4 dan Bax beserta langsung peningkatan ekspresi IL-4 terhadap sel yang mengekspresikan, (4) pemeriksaan faktorpenurunan apoptosis limfosit (r= -0,11) adalah lebih faktor lain yang kemungkinan mempengaruhi besar dibandingkan peran tidak langsung ekspresi apoptosis limfosit, antara lain: IFN-γ, Fas/Fas-L, Bak, IL-4 melalui jalur Bax limfosit (r=-0,006).…”