Altered apoptosis in bronchoalveolar lavage lymphocytes after allergen exposure of atopic asthmatic subjects

Abstract

The increased number of lymphocytes in airways during an asthmatic response is believed to be the result of increased recruitment of these cells. However, it is possible that a decreased apoptotic rate could also contribute to the increased number. The aim of the present study was to investigate whether allergen airway provocation influences the apoptotic phenotype of lung and peripheral blood lymphocytes (PBL) in subjects with atopic asthma.Bronchoalveolar lavage (BAL) lymphocytes and PBL from 12 asthmatic subjects previously challenged with allergen (n57) or saline (n55) were exposed to the apoptotic stimulus tributyltin (TBT) in vitro and assayed for apoptosis.Airway allergen provocation resulted in decreased sensitivity of BAL lymphocytes to TBTinduced apoptosis, with 42.2% (range 33.9-62.5%) apoptotic cells before challenge versus 23.5% (range 15.3-42.4%) after challenge, while PBL were unaffected. The increased apoptosis resistance correlated with higher numbers of Bcl-2-expressing lymphocytes. Interestingly, baseline caspase-3-like activity was significantly elevated in viable BAL lymphocytes compared with viable PBL, and was unaltered by allergen exposure.In conclusion, allergen inhalation renders bronchoalveolar lavage lymphocytes more resistant to apoptosis while peripheral blood lymphocytes were not influenced at all, indicating that the apoptotic phenotype of airway lymphocytes may play a role in asthmatic inflammation.

Increased apoptosis of CD4 and CD8 T lymphocytes in the airways of horses with recurrent airway obstruction

“…In addition, basal levels of apoptotic activity were significantly lower in BALL from asthmatic subjects compared with peripheral blood lymphocytes from the same subjects. These data indicate that airway inflammation in asthma is associated with a reduced susceptibility to apoptosis, which may lead to enhanced survival of lymphocytes in the bronchial mucosa and prolonged inflammation (Müller et al 2006). Other molecules are involved in the programmed cell death process, including members of the Bcl-2 gene family, which are known to inhibit apoptosis.…”

“…Apoptosis has emerged as a major mechanism in the clearance of activated T cells during the resolution of an inflammatory response (Akbar and Salmon 1997). Inadequate T cell apoptosis in asthma patients appears to interfere with normal T cell elimination, resulting in T cell accumulation, which contributes to chronic inflammation and may be the major underlying cause for tissue damage, remodeling and repair (Müller et al 2006;Vignola et al 2000). Spinozzi et al (1998) reported that pulmonary T cells isolated from BALF of atopic asthma patients showed hypoexpression of Fas and FasL; this result may explain the low frequency of apoptosis in this group of patients.…”

Activation of CXCL12/CXCR4 renders colorectal cancer cells less sensitive to radiotherapy via up-regulating the expression of survivin

“…The activation of caspase-9 subsequently increases the activity of caspase-3 (the executor of cell apoptosis). [25][26][27] In the present study, our results showed that radiotherapy facilitated the expression of Bax and led to the increased activity of caspase-9 and caspase-3, whereas these pro-apoptotic changes induced by radiotherapy were attenuated by treatment with exogenous CXCL12. Moreover, CXCR4 inhibition enhanced cellular apoptosis induced by radiation exposure.…”

Allergic Airway Inflammation

“…In addition, basal levels of apoptotic activity were significantly lower in BALF lymphocytes from asthmatic subjects compared with peripheral blood lymphocytes from the same subjects. These data indicate that airway inflammation in asthma is associated with a reduced susceptibility to apoptosis, which may lead to enhanced survival of lymphocytes in the bronchial mucosa and prolonged inflammation (Müller et al 2006). Other molecules are involved in the programmed cell death process, including members of the Bcl-2 gene family, which are known to inhibit apoptosis.…”

“…Apoptosis has emerged as a major mechanism in the clearance of activated T cells during the resolution of an inflammatory response (Akbar and Salmon 1997). Inadequate T cell apoptosis in asthma patients appears to interfere with normal T cell elimination, resulting in T cell accumulation, which contributes to chronic inflammation and may be the major underlying cause for tissue damage, remodeling and repair (Müller et al 2006;Vignola et al 2000). Spinozzi et al (1998) reported that pulmonary T cells isolated from the BALF of atopic asthma patients showed hypoexpression of Fas and FasL; this result may explain the low frequency of apoptosis in this group of patients.…”