Article: Czestsza apoptoza limfocytów pecherzykowych (alveolar lymphocytes, AL) u palaczy papierosów zalezy od ekspresji BCL-2 i swoistej odpowiedzi na czynnik martwicy nowotworów alpha (tumor necrosis factor alpha, TNFalpha). Analiza materiału z płukania oskrzelowo-pecherzykowego (bronchoalveolar lavage, BAL) chorych z wybranymi chorobami śródmiazszowymi pluc i osób zdrowych.
2012 Volume 69, Issue 10, Page(s) 731–736
Abstract: Background: We have previously described the increased apoptosis rate in smokers alveolar lymphocytes (AL) that was independent from the FASL/ FAS system activation. Consequently, the role of intrinsic apoptosis pathway and other ligand/death receptor ... ...
| Title translation | Higher incidence of alveolar lymphocytes (AL) apoptosis in smokers depends on BCL-2 expression and specific response to tumor necrosis factor alpha (TNFalpha). Bronchoalveolar lavage (BAL) material analysis from selected interstitial lung diseases (ILD) and healthy controls. |
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| Abstract | Background: We have previously described the increased apoptosis rate in smokers alveolar lymphocytes (AL) that was independent from the FASL/ FAS system activation. Consequently, the role of intrinsic apoptosis pathway and other ligand/death receptor pairs as TNFalpha/TNFR1 and TRAIL/DR4 important for apoptosis regulation should be considered in this phenomenon. The purpose of the study was to evaluate the impact of tobacco consumption on expression of selected BCL-2 family members and ligand/receptors pairs in bronchoalveolar lavage (BAL) harvested from patients with pulmonary sarcoidosis (PS), idiopathic pulmonary fibrosis (IPF) and healthy volunteers. The results were analyzed in the context of AL apoptosis rate. Methods: AL apoptosis from PS (n=36, incl. 22 smokers), IPF (11, incl. 5 smokers) and controls (n=17, incl. 9 smokers) was evaluated by flow cytometry (sub-G1 of cell cycle). AL were stained for BCL-2, BCL-xL, BAK, TNFR1 (CD120A) TNFR2 (CD120B) and DR4. ELISA assay was used to evaluate the BAL supernatant levels of TNFalpha and TRAIL. Results: According to previous observations, AL apoptosis rate was significantly higher in smoker subgroups as compared to nonsmoking counterparts. Decreased AL BCI-2+ relative number was observed in smoking PS (80.5 +/- 6.2 vs 91 +/- 9.8% in nonsmokers) and controls (59 +/- 14.1% vs 75 +/- 16.1%, p<0.05). TNFalpha concentration in BAL supernatant was significantly higher only in healthy smokers (2.32 +/- 0.77 vs 0.42 +/- 0.27 pg/ml, p<0.05), whereas TRAIL levels were remarkably enhanced in IPF smokers (44.8 +/- 12.8 vs 13.5 +/- 5.0 pg/ml, p<0.05) only. However, TUNEL. detected AL apoptosis positively correlated with TNFalpha. in smokers (p<0.05) and negatively with AL CD120B:CD120A expression ratio. Paradoxically, TNFalpha levels were positively correlated with AL BCL-2 expression in nonsmokers (Rs +0.58, p<0.01), but not in smokers. No differences were observed in all subgroups in respect to AL expression of DR4, BCL-xL or BAK. Conclusions: 1. AL were not sufficiently protected against apoptosis in smokers. 2. The most likely mechanisms involve down-regulation of BCL-2 expression and altered AL susceptibility to TNFalpha, mediated by imbalance between AL membrane expression of TNF receptor type 1 (death receptor) and type 2 (survival mediator). 3. Mechanisms regulating the increased AL apoptosis in smokers seem to be different in each tested group. |
| MeSH term(s) | Apoptosis ; Bronchoalveolar Lavage Fluid/cytology ; Down-Regulation ; Flow Cytometry ; Humans ; Idiopathic Pulmonary Fibrosis/etiology ; Idiopathic Pulmonary Fibrosis/metabolism ; Idiopathic Pulmonary Fibrosis/pathology ; Lymphocytes/metabolism ; Lymphocytes/pathology ; Reference Values ; Sarcoidosis, Pulmonary/etiology ; Sarcoidosis, Pulmonary/metabolism ; Sarcoidosis, Pulmonary/pathology ; Smoking/adverse effects ; Smoking/metabolism ; Smoking/pathology ; Tumor Necrosis Factor-alpha/metabolism ; bcl-2-Associated X Protein/metabolism |
| Chemical Substances | Tumor Necrosis Factor-alpha ; bcl-2-Associated X Protein |
| Language | Polish |
| Publishing date | 2012 |
| Publishing country | Poland |
| Document type | English Abstract ; Journal Article |
| ZDB-ID | 414053-9 |
| ISSN | 0033-2240 ; 0860-0422 |
| ISSN | 0033-2240 ; 0860-0422 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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