The programmed death of alveolar lymphocytes is elevated in idiopathic pulmonary fibrosis (IPF). The plausible explanation of well-known bronchoalveolar lavage cytological findings?

Abstract

Background: T cells are considered to protect lung tissue from fibrosis in interstial lung diseases (ILD) complicated with fibrosis, in opposite to bad-prognostic BAL neutrophilia, however the neutrophils paradoxally seem to degradate pulmmonary connective tissue, incl. collagen and elastine.

Examination of AL apoptosis rate in IPF and non-specific interstitial pneumonia (NSIP), witth special attention to NSIP fibrotic form. Results assessment in context of large range of clinical data and BAL cytoimmunological pattern.

Methods: BAL of patients with IPF (n=17), NSIP (n=11) and 9 controls (all nonsmokers) was examined for: a) cytoimmunology, b) AL apoptosis with flow cytometry (sub-G1 peak of cell cycle, scatter properties of CD4+ and CD8+ cells separately); c) TUNEL assay; d) AL staining for BCL-2, caspase-3, death receptors (DRs) and their ligands (FasL, TRAIL).

Results: AL apoptosis was higher in patients than in controls (TUNEL: 32.8±14.2 for IPF and 27.5±10.1 vs 11.3±4,9%, median±SEM, p<0.05). IPF was characterized by remarkably lower AL BCL-2+ percentage, higher caspase-3 and FasL expression. AL apoptosis rate in IPF and NSIP was correlated negatively with BAL lymphocytosis (Rs=–0.33, p<0.05), DLCO (Rs=–0.71, p<0.01) and VC pred. values (Rs=–0.68, p<0.01) and, the most interesting, very strongely positively with BAL neutrophilia (Rs=–0.5, p<0.0001); analogous statistic tendency was also found in controls.

Conclusion: We supported some new evidence for protective AL role in fibrotic ILD. Neutrophils may cause fibrosis indirectly, inducing AL apoptosis by free radicals or other inflammatory mediators.