Increase of lung neutrophils in hypersensitivity pneumonitis is associatedwith lung fibrosis

Hypersensitivity pneumonitis (HP) is characterized by a T-cell-mediated alv eolitis, and the putative role of other inflammatory cells in its pathogene sis remains unclear. In this study we determined whether increased quantiti es of neutrophils were present in HP lungs, and if they were positive for g elatinase B and collagenase-2. Fifteen nonsmoking patients with subacute/ch ronic active HP were included. Lung samples were analyzed using myeloperoxi dase antibody, and neutrophil/total cell ratio was evaluated by digital pro cessing. All HP tissue samples exhibited variable quantities of neutrophils located inside vessels, and in the interstitial and alveolar spaces. Lung neutrophil percentage ranged from 0.7% to 4.8% (2.1 +/- 1.4%). There was a positive correlation between the percentage of lung neutrophils and the per centage of lung fibrosis (r = 0.6, p < 0.02). Tissue neutrophils showed int ense immunoreactive collagenase-2 and gelatinase B staining. Additionally, gelatinolytic activities corresponding to progelatinases A and B and their activated forms, were several-fold increased in the bronchoalveolar lavage fluid (BALF) from patients with HP as compared with control subjects. These findings suggest that in HP lungs there is a persistent traffic of neutrop hils loaded with gelatinase B and collagenase-2 that may play a role in the lung damage and in the fibrotic response.