Elastase secretion by stimulated macrophages. Characterization and regulation.

Abstract

Thioglycolate-stimulated mouse peritoneal macrophages secrete a Proteinase which degrades insoluble elastin. There is little elastase activity in cell lysates but the bulk of the enzyme accumulates extracellularly during culture in serum-free medium. The secretion of elastase is sustained for over 12 days in culture and continued secretion of elastase requires protein synthesis. Unstimulated macrophages secrete very little elastase activity but can be triggered to secrete higher levels of this enzyme by phagocytosis and intracellular storage of latex particles. The macrophages elastase is a distinctive proteinase differing from the elastases of pancreas and granulocytes and is distinct from the other secreted proteinases of macrophages, namely, collagenase and plasminogen activator. The macrophages elastase is a serine proteinase and is inhibited by di-isopropyl phosphoro-fluoridate, ovoinhibitor, EDTA, dithiothretiol, and serum. Its activity is little affected by soybean trypsin inhibitor, turkey ovomucoid and chloromethyl ketones derived from tosyl lysine, tosyl phenylalanine, and acetyltetra alanine. Hydrolysis by macrophage elastase of chromogenic ester substrates for pancreatic elastase could not be detected. Elastase secretion by stimulated macrophages exceeds that by primary and established fibroblast cell strains. It is likely that elastase secretion by macrophages plays a major role in the pathogenesis of chronic destructive pulmonary diseases such as emphysema.

Macrophage stimulation by bacterial lipopolysaccharides. I. Cytolytic effect on tumor target cells.

“…1 a). However, elicited macrophages differ significantly from the resident peritoneal macrophage population in their morphologic, biochemical, and functional attributes and apparently represent a more differentiated cell population (14,(28)(29)(30)(31)(32). In this report, we have demonstrated that LPS stimulates further differentiation in elicited macrophages resulting in cellscapable of killing tumor cells.…”

Neutral protease secretion by human monocytes. Effect of surface-bound immune complexes.

“…The elastase found in conditioned medium from mouse peritoneal macrophages is not inhibited by STI and it is secreted in a continuous fashion (5). Monocytes stain weakly with naphthol AS-D chloroacetate (39), a histochemical substrate for leukocyte elastase and cathepsin G (40).…”

Overexpression of Human Matrix Metalloproteinase-12 Enhances the Development of Inflammatory Arthritis in Transgenic Rabbits

“…1,2 Among MMPs, MMP-12, also known as macrophage elastase (HME), is the predominant MMP produced by macrophages. 3,4 Accumulating evidence has shown that increased activity of MMP-12 secreted from inflammatory macrophages is associated with several destructive diseases, including atherosclerosis, 5 aortic aneurysm formation, 6 and emphysema. 7 Although the major substrate for MMP-12 is elastin, MMP-12 is able to degrade a broad spectrum of substrates such as type IV collagen, fibronectin, laminin, vitronectin, proteoglycans (PGs), chondroitin sulfate, myelin basic protein, ␣-1-anti-trypsin, and plasminogen.…”