[Apoptosis of alveolar lymphocytes in sarcoidosis and in control group is more frequent in smokers than in nonsmoking persons].
Cigarette smoking enhances apoptosis rate of alveolar macrophages. However, little is known about the appearance and extension of apoptosis in bronchoalveolar lavage (BAL) lymphocytes originating from smoker individuals, both in pulmonary sarcoidosis (the disease characterized by lymphocytic alveolitis) and in controls. BAL was carried out in 60 nontreated patients with pulmonary sarcoidosis, subdivided acc. smoking status and in 22 control persons, free of any lung pathology. BAL (alveolar) lymphocytes were a) stained for TUNEL; b) permeabilized and stained with PI for late apoptosis/cell cycle analyses; c) immunophenotyped, including CD95, CD95 Ligand, Bcl-2, Bcl-XL, Bak and insulin-like growth factor-I (IGF-I) expression. BD FACSCalibure flow cytometer, PC Lysys and ModFit software were applied. The low number of AL entered apoptosis, which was confirmed by both techniques. Cigarette smokers were characterized by higher AL apoptosis percentage in respective subgroups (sarcoidosis: 0.6 +/- 0.13 in nonsmokers vs 0.9 +/- 0.23 in smokers; controls: 0.85 +/- 0.23 in nonsmokers vs 1.5 +/- 0.35 smokers, median +/- SEM, p < 0.05); the proliferation rate was lower. Decreased IGF-I expression in AL of sarcoidosis smokers was observed (13.5 +/- 9.2 vs 46.0 +/- 6.0 in nonsmokers, p < 0.05). No differences were found between studied groups in expression of Bcl-2, Fas and FasL molecules (except significantly declined ratio of CD8+FasL+ cells in sarcoidosis nonsmokers). AL apoptosis rate was positively correlated with respective alveolar macrophage results (Rs = +0.59, p < 0.00001) and negatively with CD4/CD8 ratio (Rs = -0.32, p < 0.001); no correlation was found with lung function test results and with Bcl-2, Fas and FasL expression in BAL cells. Apoptosis of alveolar lymphocytes was more frequent in nonsmokers both in pulmonary sarcoidosis and in controls; lower AL percentage proliferates. These phenomena seem to participate in lower AL percentage, observed in smoker subgroup of sarcoidosis. Some mechanisms of local apoptosis alterations in smokers may be common for alveolar lymphocytes and macrophages.
Kopiński
Piotr
P
Katedra Terapii Genowej, CM UMK, Bydgoszcz. kizgenoter@cm.umk.pl
Przybylsk
Grzegorz
G
Balicka-Slusarczyk
Barbara
B
Jarzemska
Agnieszka
A
Dyczek
Andrzej
A
Pinis
Grazyna
G
Bartczak
Karina
K
Plato
Marta
M
Jankowski
Marek
M
Szczeklik
Jerzy
J
D017209:Apoptosis; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology*; D016516:CD4-CD8 Ratio; D002453:Cell Cycle; D053222:Fas Ligand Protein / Q000032:analysis; D006801:Humans; D016130:Immunophenotyping; D020287:In Situ Nick-End Labeling; D008214:Lymphocytes / Q000737:chemistry / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D011650:Pulmonary Alveoli / Q000473:pathology*; D017565:Sarcoidosis, Pulmonary / Q000473:pathology*; D012907:Smoking / Q000473:pathology*; D019014:fas Receptor / Q000032:analysis
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor