Neutrophil activation in fibrosing alveolitis: a comparison of lone cryptogenic fibrosing alveolitis and systemic sclerosis

Abstract

Fibrosing alveolitis complicating systemic sclerosis (FASSc) carries a better prognosis than lone cryptogenic fibrosing alveolitis (CFA). We wanted to determine whether this improved prognosis is associated with differential neutrophil migration and activation in the lower respiratory tract.We therefore compared bronchoalveolar lavage (BAL) neutrophil numbers and levels of neutrophil-derived enzymes in FASSc, CFA and normal individuals. Bronchoalveolar lavage was performed on 45 subjects (FASSc n=20; CFA n=15; normals n=10); cell counts and levels of neutrophil-derived enzymes, myeloperoxidase, elastase (total elastase and elastase/α 1 -antitrypsin complexes), collagenase and lactoferrin were measured. Lung function testing was performed in subjects with fibrosing alveolitis.Significant differences in the levels of collagenase, myeloperoxidase and elastase/ α 1 -antitrypsin complexes were present in the BAL fluid from the three groups. Patients with CFA had significantly higher neutrophil percentages and levels of collagenase and myeloperoxidase than those with FASSc. Disease extent, as judged by lung volumes and gas transfer, was comparable in the CFA and FASSc groups. Forced vital capacity (% predicted) was significantly lower in patients with evidence of increased neutrophil enzyme release than those without.We conclude that: 1) increased neutrophil migration to the lung is accompanied by release both of primary and secondary granule enzymes in cryptogenic fibrosing alveolitis; and 2) the lower amounts of neutrophil products in fibrosing alveolitis complicating systemic sclerosis may account for the improved prognosis, even when disease is as extensive as in cryptogenic fibrosing alveolitis. Eur Respir J., 1996, 9, 992-999.

Differential Role of Neutrophils and Alveolar Macrophages in Hepatocyte Growth Factor Production in Pulmonary Fibrosis

“…We obtained similar results when we studied HGF secretion by alveolar neutrophils obtained from ventilated patients with acute lung injury (Jaffre et al, 2002). We hypothesize that the lack of response to LPS is a result of the degranulation of neutrophils when migrating to the alveolar space as previously suggested by others (Cailes et al, 1996). Further studies are needed to confirm this hypothesis.…”

Neutrophil chemotaxis in granulomatosis with polyangiitis (Wegener's) and idiopathic pulmonary fibrosis

“…CXCL8 is known to have potent chemotactic activity and has an important role in the accumulation of neutrophils in the lungs of patients with IPF [27] and adult respiratory distress syndrome [28], where persistent neutrophilia is associated with mortality. CXCL8 is able to increase neutrophil adhesiveness and upregulate intercellular adhesion molecule-1 IL-1b pg?mL expression, potentially promoting margination [16].…”

Elevated levels of leukotriene B4 and leukotriene E4 in bronchoalveolar lavage fluid from patients with scleroderma lung disease

“…In addition, several studies have shown that increased numbers of neutrophils in BAL fluid were associated with more severe lung disease (35,36,40). This effect is probably caused by an increased release of proteolytic enzymes and oxygenderived radicals, which in turn, may contribute to the degradation of lung parenchyma (40). In vitro studies have shown that LTB 4 activates neutrophils, which leads to their degranulation, and may therefore contribute to the progression of SLD (18,19).…”

“…and the application of LTB 4 results in rapid influx of neutrophils into the lungs (14). In addition, several studies have shown that increased numbers of neutrophils in BAL fluid were associated with more severe lung disease (35,36,40). This effect is probably caused by an increased release of proteolytic enzymes and oxygenderived radicals, which in turn, may contribute to the degradation of lung parenchyma (40).…”