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

Abstract

The effect of surface-bound immune complexes on the secretion of neutral proteases by human peripheral monocytes was examined. Monocytes cultured on 125I-fibrin secreted plasminogen activator in a continuous fashion. Monocytes incubated on 125I-fibrin with surface-bound immune complexes displayed a burst of plasminogen-independent fibrinolytic activity, whereas no release of plasminogen activator was observed through 21 h. The plasminogen-independent fibrinolytic enzymes were derived from monocytes and not from lymphocytes or contaminating polymorphonuclear neutrophils. The effects of various protease inhibitors on the secretion of plasminogen-dependent and independent enzymes were determined. Chymostatin selectively inhibited the monocyte-derived plasminogen activators. Similar effects of chymostatin were observed on human urokinase in the absence of cells. The predominant protease producing plasminogen-independent fibrinolysis exhibited responses to inhibitors characteristic of leukocyte elastase. When monocytes were cultured on 125I-fibrin with adherent immune complexes approximately equal to 40% of the solubilized radioactivity represented deiodination and not proteolysis. It was concluded that culture of human monocytes on surface-bound immune complexes stimulates the secretion of plasminogen-independent fibrinolytic proteases, primarily elastase, and of deiodinating enzymes. Under these conditions, plasminogen activator secretion is inhibited. Neutral proteases secreted from newly recruited monocytes may contribute to tissue injury in human diseases characterized by the presence of adherent immune complexes.

Loss of Fc receptor activity after culture of human monocytes on surface-bound immune complexes. Mediation by cyclic nucleotides.

“…Fc receptor activity could not be reduced by incubating MNL with substrates that contained high amounts of antigen, a surface-bound phagocytic stimulus that leads to the same degree of protease activity elicited by adherent immlme complexes (4). Inactivation of superoxide anion and hydrogen peroxide by SOD and catalase did not prevent the loss of EA rosetting by monocytes incubated on complex-containing substrates.…”

“…This loss in EA rosetting was seen as early as 30 min after plating of MNL onto complexes. Reduced rosetting persisted through 21 h of culture in 10% FCS; during this time the cells also lost viability (4). When plates were sensitized with F(ab')2 anti-HSA, 78% of the adherent cells formed EA rosettes.…”

Elastase of U-937 Monocytelike Cells

“…These macrophage elastases are calcium dependent, inhibited by EDTA, unaffected by inhibitors of serine proteinases, and without activity against synthetic elastase substrates such as SLAPN and MSAPN (7,43,44). The catalytic features of U-937 elastase are noteworthy for at least two reasons: (a) they match elastase activity of human monocytes described in several reports and (b) they provide further evidence that serine proteases with elastase activity are associated with human mononuclear phagocytes (8,9). (9) found that monocytes show more than one form of elastase in SDS-polyacrylamide gel electrophoresis autofluorograms using radiolabeled chloromethylketone elastase inhibitors.…”

“…Recent information suggests that monocytes have elastolytic activity that shares catalytic features with neutrophil elastase rather than with murine macrophage elastase (8,9). These data are noteworthy for at least two reasons: (a) they are further evidence for developmental alterations in monocytes during differentiation into macrophages (10)(11)(12), and (b) they indicate another source of elastolytic activity that could be active whenever there is insufficient alpha-1-proteinase inhibitor or when alpha-l-proteinase inhibitor has been oxidatively inactivated (13).…”

Human Monocytes Release Plasma Serine Protease Inhibitors in vitro

“…They are a potent source of the procoagulant activities starting the coagulation cascade [1,2] and of the tis sue plasminogen activator triggering the fi brinolysis process [5,11], Elicited or acti vated macrophages also synthesize greatly enhanced amounts of neutral proteases [12]. Taken together, monocytes and macro phages are responsible for both local fibrin deposition and resorption which play an im portant role in tissue destruction in human diseases.…”