Assessment of granulomatous inflammations by lysosomal enzymes

Abstract

Granulomas are focal, predominantly mononuclear tissue inflammations evoked by persistent irritants. Granulomatous inflammation can be classified as either a hypersensitive type (immunologic) or a foreign-body type (non-immunologic) response. The common histopathologic feature, predominant infiltra-tion of mononuclear cells, is observed in both types of lesions. Granulomatous inflammation has been difficult to study because existing assays were subjec-tive, time consuming, or only indirectly reflected changes in the lungs. Macrophages secrete a wide range of biologically active mediators such as cytokines and lysosomal enzymes in response to inflammatory stimuli. The purpose of this study was to determine whether lysosomal enzyme activities correlates with sizes of lung granulomas that are composed predo-minantly of macrophages. Foreign-body (dextran beads) and hypersensitivity (antigen-coupled agarose beads) lung granulomas were induced in BALB/c mice by the intratracheal injection of artificial micro-particles. Large granulomas developed, which reached peak intensity within 3 days and declined in size thereafter. Aqueous extracts of both granulomas contained a large amount of lysosomal enzymes N-acetyl-β-D-glucosaminidase and lysozyme. Lysosomal enzyme activities in the extracts correlated with granuloma sizes. Dispersed granuloma cells were able to produce these enzymes. These results suggest that lysosomal enzymes may reflect the activity/size of granulomatous inflammation.