Hydrolytic enzyme of the alveolar macrophage in diffuse pulmonary interstitial disease

Abstract

Hydrolytic enzymes [acid phosphatase, β-glucuronidase, β-D-N-acetyl glucosaminidase (β-D-NAGA), lysozyme and angiotensin-converting enzyme (ACE)] are the major constituents of alveolar macrophages (AM). These enzymes play a crucial role in the pathogenesis of interstitial lung diseases. Cell-associated activity of several enzymes in alveolar macrophages obtained from control subjects ( n=5) and patients suffering five representative types of interstitial pulmonary diseases [sarcoidosis ( n=10), extrinsic allergic alveolitis ( n=5), idiopathic pulmonary fibrosis ( n=5), neoplastic infiltration of the lung ( n=5) and Pneumocystis carinii pneumonia ( n=5)] were evaluated. Cells were obtained by bronchoalveolar lavage and isolated by Ficoll-Hypaque gradient. Enzymatic activity was assessed by standardized tests. Bronchoalveolar lavage (BAL) lymphocyte counts were significantly elevated in the patients with active sarcoidosis (median: 57%), allergic extrinsic alveolitis (median: 51%) and neoplasic infiltration (median: 31%) as compared with the other groups, whereas BAL neutrophil and eosinophil counts were significantly elevated in the patients with idiopathic pulmonary fibrosis (neutrophil median: 29%; eosinophil median: 3%). The highest alveolar macrophage enzymatic activities were obtained in the active sarcoidosis group (median ACE: 23·38 μKat 10 −6 AM; median lysozyme: 8·64 nKat 10 −6 AM; median β-glucuronidase: 324·22 U 10 −6 AM; median acid phosphatase: 0·78 nKat 10 −6 AM; median β-D-NAGA: 1·85 nKat 10 −6 AM) which was significantly greater than in the control group (median ACE: 6·69 μKat 10 −6 AM; median lysozyme: 1·95 nKat 10 −6 AM; median β-glucuronidase: 39·88 U 10 −6 AM; median acid phosphatase: 0·38 nKat 10 −6 AM; median β-D-NAGA: 0·44 nKat 10 −6 AM). However, intracellular lysosomal enzymatic activities of alveolar macrophages from patients with allergic extrinsic alveolitis, a disease in which the degree of alveolar macrophage activation is maximal, were similar to those of the control group. These findings demonstrated a different pattern of expression of alveolar macrophage's hydrolytic enzymes in lymphocytic diffuse pulmonary interstitial disease. In sarcoidotic patients, hydrolytic enzymes were increased whereas in allergic extrinsic alveolitis, hydrolytic enzyme activities were similar to control groups. Indirect data suggest that the release of lysosomal enzymes by alveolar macrophages during allergic extrinsic alveolitis may be a factor involved in the pulmonary lesions appearing in this disease.