Abstract
Background: The implication of T cells in IPF pathogenesis is controversial. The views vary from direct lymphocytes participation in lung fibrosis to their protective role against the process.
Aim: Examination of AL apoptosis frequency in IPF. Results were related to clinical data and BAL cytoimmunological pattern, in order to evaluate the physiopathological role of AL and T cell apoptosis mechanisms in IPF.
Methods. BAL of 27 IPF patients and 17 controls was examined for: a) cytoimmunology, b) supernatant levels of cytokines taking part in cell apoptosis/survival (ELISA), c) AL apoptosis with flow cytometry (sub-G1 peak of cell cycle); d) TUNEL assay; e) AL staining for BCL-2, BCL-xL, BAK, caspase-3, and death receptors (DRs).
Results. In all methods AL apoptosis was higher in IPF than in controls (sub-G1 peak: 2.8±2.2 vs 1.0±0,2%, p<0.05). IPF was characterized by remarkably lower AL BCL-2+ percentage, higher caspase-3 and death receptor TNFR1 expression. TNFα and soluble FAS levels were increased in supernatants; there was no difference in IL-7 and TRAIL expression. AL apoptosis rate in IPF was correlated negatively with BAL lymphocytosis (Rs=–0.35, p<0.02) and positively with BAL neutrophile percentage (Rs=–0.51, p<0.001), as well as both DLCO (Rs=–0.77, p<0.01) and VC pred. values (Rs=–0.88, p<0.001).
Conclusions. AL protect lung tissue from fibrosis; AL apoptosis is an unfavourable process and its inhibition should be considered as important therapeutic option in IPF. Its mechanisms may include BCL-2 family proteins interaction, and TNFα:TNFR1 ligation. The way that neutrophiles impact AL apoptosis needs further explanation.
- © 2013 ERS