Macrophages are activated by endocytosis of α2-macroglobulin-protease complexes to produce neutral proteases

Vischer, Thomas L.; Berger, D.; Flory, Elisabeth

doi:10.1007/978-94-010-9423-8_123

Cited by 2 publications

(2 citation statements)

References 9 publications

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“…For example, macrophages (M4) have receptors that can bind and internalize certain lipophilic apoproteins, maleylated or acetylated proteins, a-2-macroglobulin (a2M) complexed to proteases, and fucose or mannose terminal glycoproteins (1)(2)(3)(4). Such receptors are believed to be important in homeostasis because they facilitate uptake of various macromol- ecules, such as lysosomal enzymes, antigen-antibody complexes, protease-protease inhibitor complexes, low-density lipoproteins (LDL), and modified-LDL (1)(2)(3)(4).…”

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confidence: 99%

Receptors for Maleylated Proteins Regulate Secretion of Neutral Proteases by Murine Macrophages

Johnson

Pizzo

Imber

et al. 1982

Science

104

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Receptors for maleylated or acetylated proteins as well as for alpha-2-macroglobulin-protease complexes on macrophages serve as scavengers by mediating the uptake of macromolecules from the extracellular compartment. Described in this report is a novel function of these receptors on macrophages: regulation of neutral protease secretion. The binding of maleylated bovine serum albumin to macrophages triggered secretion of three neutral proteases: neutral caseinases, plasminogen activator, and cytolytic proteinase. Release of acid phosphatase, however, was not induced. An important biological consequence of protease secretion by macrophages, tumor-cytolysis, was also triggered by engagement of the receptor for maleylated bovine serum albumin. By contrast, the binding of alpha-2-macroglobulin-protease complexes to the macrophages suppressed secretion of all three proteases. Thus two receptors heretofore believed to serve principally as scavengers also regulate secretory functions of macrophages.

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confidence: 99%

Receptors for Maleylated Proteins Regulate Secretion of Neutral Proteases by Murine Macrophages

Johnson

Pizzo

Imber

et al. 1982

Science

104

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“…After release of elastase phages in liver and spieen (13). It has been shown into the extracellular space, this catipnic serine pro-that fixed macrophages are activated by endocytosis of proteinase-a 2 -macroglobulin complexes to produce and secrete neutral proteinases (14) and probably prostaglandins. Thus, the disposal of elastase-a 2 -macroglobulin complexes seems to be a way of amplifying inflammation and might be involved in the Stimulation of hepatic acute phase protein synthesis (15).…”

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confidence: 99%

Pathobiochemical Significance of Granulocyte Elastase Complexed with Proteinase Inhibitors: Effect on Glycosaminoglycan Metabolism in Cultured Synovial Cells

Kleesiek¹,

Leur²,

Reinards³

et al. 1987

Clinical Chemistry and Laboratory Medicine

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Summary:Interactions between elastase Inhibitor complexes and synovial cells are of special interest, since, in chronic joint diseases, granulocytes release large amounts of elastase into the synovial fluid and connective tissue, where the proteinase is böund to cti-proteinase inhibitor and a 2 -macroglobulin. To study the effect of elastase-a 2 -macroglobulin and elastase-a r proteinase inhibitor complexes on the glycosaminoglycan metabolism of cultured synovial cells, we determined the distribution of [ 3 H]glucosamine-labelled hyaluronate, which represents the main synthesized glycosaminoglycan, and of 35 SO4~-labelled chondroitin sulphate into the intracellular, pericellular and extracellular compartments of the cell culture. Exposure of the synovial cells to elastase-a 2 -inacroglobulin complexes leads to an enhanced synthesis and secretion of hyaluronate and chondroitin sulphate, and also induces a rise of the fibronectin concentration in the medium. Analogous but less pronounced effects are observed in the presence of elastase-a r proteinase inhibitor complexes. Native uncomplexed elastase, however, causes no significant changes in hyaluronate metabolism. An increase of prostaglandin E 2 in the culture medium during incubation with elastase inhibitor complexes occurs in parallel to the stimulatory effect on glycosaminoglycan metabolism. Our results demonstrate that elastase, whose enzymic activity is inactivated by the formation of complexes with fy -proteinase inhibitor or a 2 -macroglobulin, nevertheless acts äs an inflammatory mediator, which in vitro induces metabolic changes closely resembling the in vivo findings in inflammatory joint diseases.

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Macrophages are activated by endocytosis of α2-macroglobulin-protease complexes to produce neutral proteases

Cited by 2 publications

References 9 publications

Receptors for Maleylated Proteins Regulate Secretion of Neutral Proteases by Murine Macrophages

Receptors for Maleylated Proteins Regulate Secretion of Neutral Proteases by Murine Macrophages

Pathobiochemical Significance of Granulocyte Elastase Complexed with Proteinase Inhibitors: Effect on Glycosaminoglycan Metabolism in Cultured Synovial Cells

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