Cell
Volume 8, Issue 2, June 1976, Pages 271-281
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Article
Macrophage plasminogen activator: Modulation of enzyme production by anti-inflammatory steroids, mitotic inhibitors, and cyclic nucleotides

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Abstract

Plasminogen activator production by cultured mouse peritoneal macrophages can be modulated in vitro by low concentrations of various pharmacologically active molecules. Glucocorticoid hormones and their synthetic derivatives, as well as cholera toxin, colchicine, and vinblastine markedly inhibit production of this enzyme without affecting other important macrophage functions. The effect of glucocorticoids is of particular interest, both because their relative in vivo anti-inflammatory potencies correlate exactly with their effect on plasminogen activator production in culture and because this effect occurs at near physiological concentrations.

In view of the correlations established in other systems between plasminogen activator production and cell migration, we have also examined the age of the macrophages in thioglycollate-induced exudates. Confirming the results of Van Furth and Cohn (1968), we have found that the majority of these cells are young, having recently replicated and arrived in the peritoneal cavity. Using a fibrinagar overlay technique which allowed us to determine the production of plasminogen activator by individual cells, we have also found that the majority of these cells produce the enzyme. The potential roles of plasminogen activator in monocyte migration and the relationship of this enzyme to the anti-inflammatory effect of glucocorticoids are correlated and emphasized.

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    Present address: Memorial Sloan-Kettering Cancer Center, New York, New York 10021.

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