Role of mast cells in the pathogenesis of hypersensitivity pneumonitis.

Abstract

To examine the possibility that mast cells have a central role in the pathogenesis of hypersensitivity pneumonitis, 20 patients with this disease were studied with the aim of seeking evidence for mast cell degranulation.The number of mast cells recovered by bronchoalveolar lavage from patients with hypersensitivity pneumonitis was more than 1000 times greater than those recovered from normal individuals. Furthermore, discontinuation of antigen exposure resulted in an increase in the number of mast cells observed, consistent with the possibility that antigen exposure had induced mast cell degranulation. Cessation of antigen exposure also resulted in a rapid decrease in the number of neutrophils and eosinophils recovered by lavage, followed by an increase in the number of T8 + T lymphocytes present. In each case the time course of the changes was consistent with the possibility that mast cell degranulation had been important in regulating the number of the immune and inflammatory cells present in the lung. Histamine was present in lavage fluid supernatant from patients with hypersensitivity pneumonitis. The amount of histamine present was, however, closely correlated with the number of mast cells present and not with the interval since last antigen exposure. Delay in separating cells from lavage fluid supernatant resulted in an increase in histamine content. These results suggest that the free histamine in lavage fluid resulted from the degranulation of mast cells induced by the lavage procedure as histamine released in vivo has a short half life. We suggest that hypersensitivity pneumonitis results from a "late phase reaction" initiated by antigen induced mast cell degranulation.

Hypersensitivity pneumonitis

“…CD56 + NK cells are increased in BAL from HP patients but this level decreases with corticosteroid treatment or antigen contact avoidance (63,97,115). Data also show an increased level of mastocytes but their role in HP is still controversial (64,116,117). Plasmocytes are also increased in HP with severe alveolitis (118).…”

“…A predominance of CD8 + T lymphocytes and a CD4 + / CD8 + ratio lower than 1 is often observed in HP whereas a high CD4 + /CD8 + ratio is related to sarcoidosis (63) suggesting that this ration could be used to differentiate HP from sarcoidosis. This is now challenged as the CD4/CD8 ratio can be increased in HP to levels as high as those seen in sarcoidosis (64)(65)(66). Recent studies suggest that this low CD4 + /CD8 + ratio is associated to the chronic form of HP and to asymptomatic individuals whereas a predominance of CD4 + T cells is related to the acute phase of the disease (67,68).…”

Migratory bronchiolitis obliterans organizing pneumonia after unilateral radiation therapy for breast carcinoma

“…Pulmonary mastocytosis is a well-documented phenomenon after lung radiation in animals [6,12], most obvious in the areas of fibrosing alveolitis, but also apparent in the lung tissue of normal-appearance in irradiated rats [13]. This suggests that mast cells could participate in the induction of radiation-induced lung injury through the release of various mediators [13,14], as suspected in the pathogenesis of hypersensitivity pneumonitis due to inhaled antigens [15]. However, the precise role of mast cells is unknown, since increased numbers of mast cells are sometimes observed in BAL in bronchiolitis obliterans organizing pneumonia not associated with irradiation [11].…”

The controversial role of mast cells in fibrosis

“…MCs are numerous in healthy airways and lung parenchyma, but are increased in the fibrotic areas of alveolar parenchyma in patients with pulmonary fibrosis resulting from several diverse aetiologies including IPF, connective tissue disease‐associated lung fibrosis, chronic hypersensitivity pneumonitis, sarcoidosis, chronic berylliosis, silicosis, bronchiolitis obliterans organizing pneumonia, Langerhans cell histiocytosis, and infants with bronchopulmonary dysplasia . Increased numbers of MCs have also been identified in the bronchoalveolar lavage (BAL) fluid of patients with various interstitial lung diseases although studies vary, and in the alveolar spaces, particularly in hypersensitivity pneumonitis and BOOP . These observations are in keeping with the original electron microscopic images taken by Kawanami et al demonstrating MCs migrating through the alveolar basement membrane in patients with IPF but not “healthy” controls.…”