Abstract
Background: The participation of AL in EAA pathogenesis is evident, since lymphocytic alveolitis is characteristic for the disease. However, it is not clear, if BAL lymphocytosis in EAA depends on migration, proliferation or apoptosis disorders.
Aim: Examination of AL apoptosis frequency in EAA. Results related to BAL cytoimmunological pattern, in order to assess the role of AL apoptosis in the disease.
Methods: BAL of 13 EAA patients and 10 controls was examined for: a) cytoimmunology; b) AL staining for BCL-2 family, kaspase-3, and death receptors (DRs); c) AL apoptosis with flow cytometry (sub-G1 peak of cell cycle); d) TUNEL assay; e) supernatant levels of cytokines taking part in cell apoptosis, incl. ligands of DRs (ELISA).
Results: AL apoptosis was lower in EAA than in controls (sub-G1 peak: 0.4±0,1 vs 1.0±0,2%, TUNEL: 9.8±9.9 vs 27.5±6,2%, p<0.05 for all, median±SEM); AL cell cycle was completely arrested. EAA was characterized by remarkably higher levels of DR ligands, i.e. TNFα, soluble TRAIL and soluble FasL, but AL superficial expression of TNF receptor 1, DR3, DR4, FasL and TRAIL was significantly lower than in controls: the distribution of the markers was similar for CD4+ and CD8+ cells. Despite low CD4/CD8 index, the frequency of apoptosis throughout CD4 and CD8 population was similar in EAA and controls. AL apoptosis rate in EAA was correlated negatively with BAL lymphocytosis (Rs=–0.38, p<0.05).
Conclusions: AL in EAA, in highly cell death inducing environment, ere protected from apoptosis, due to superficial loss of DRs and their ligands. AL infrequent apoptosis is responsible for development of lymphocytic alveolitis in EAA but seems to have no impact on CD4/CD8 index.
- Copyright ©the authors 2016