Expression of 92 kDa phagocyte gelatinase by inflammatory and connective tissue cells.
It is now apparent that multiple proteinases cooperate in the degradation of the collagenous matrix. Among these proteinases are two biochemically related proteinases which were originally identified by their ability to degrade denatured collagens. The higher molecular weight proteinase (M(r) = 92,000) is predominantly expressed by inflammatory cells while the lower molecular weight proteinase (M(r) = 72,000) is secreted constitutively by fibroblasts. To explore the expression of the 92 kDa proteinase, the gelatinase from human neutrophils was purified and characterized and specific immunologic probes developed for its study in other cell types. Studies of leukemic cell lines (U937s and HL60s) which can be differentiated to a monocyte/macrophage phenotype revealed that after differentiation with phorbol myristic acetate the 92 kDa proteinase was the major proteinase produced. Additional studies of human alveolar macrophages and monocytes differentiated in vitro suggest that these cells secrete a proteinase immunologically and biochemically similar to human neutrophil gelatinase. Although the major gelatinase secreted by the fibroblasts is the 72 kDa proteinase, they also produce the 92 kDa proteinase in a regulated manner. These studies suggest that the regulation of these similar gelatinolytic proteinases varies dependent on cell type. Further studies of their regulation will be important to define the roles of these proteinases in physiologic and pathological processes.
Hibbs
M S
MS
Division of Rheumatic Diseases, University of Connecticut Health Center, Newington.
D002454:Cell Differentiation / Q000187:drug effects; D017364:Collagenases / Q000096:biosynthesis* / Q000145:classification; D003238:Connective Tissue / Q000201:enzymology*; D004790:Enzyme Induction / Q000187:drug effects; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D007249:Inflammation; D007948:Leukemia, Monocytic, Acute / Q000473:pathology; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology; D016676:Macrophages, Alveolar / Q000201:enzymology; D020780:Matrix Metalloproteinase 9; D008970:Molecular Weight; D009000:Monocytes / Q000201:enzymology; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009504:Neutrophils / Q000201:enzymology*; D010586:Phagocytes / Q000201:enzymology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D009363:Neoplasm Proteins; D017364:Collagenases; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate