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Control of exogenous proteinases and their inhibitors at the macrophage cell surface
1Ciba-Geigy, Basel, Switzerland.
Abstract:
The actions and availability of human neutrophil elastase and its protein inhibitor, Eglin, when co-incubated with macrophages were investigated. Eglin did not induce radical production by mouse peritoneal macrophages; nor were specific binding sites for Eglin detected on these cells. Mouse peritoneal macrophages could inactivate both elastase and Eglin extensively, when these targets were used at concentrations appropriate to the extravascular fluids. Two methods were used for assessing such inactivation: one, as in previous literature, only took account of molecules remaining in the supernatant after interaction with the cells; the other (lacking from most previous studies) took into account all target molecules, including those associated with the cells. From an analysis of both types of experiment, it was shown that the cell-derived inactivators were stable products, whose quantity was not significantly influenced by the induction of a macrophage oxidative burst and its associated free radicals. They were probably mainly proteinases and proteinase inhibitors. Thus, mouse peritoneal macrophages restrict the activity of proteinases and inhibitors by means of stable molecules, such as proteins. Other mononuclear phagocytes may use free radicals and oxidants more extensively in this respect.
Insights
Mouse peritoneal macrophages inactivate human neutrophil elastase and Eglin using stable molecules, not free radicals. This mechanism limits protease and inhibitor activity in extravascular fluids.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Human neutrophil elastase (HNE) and its inhibitor Eglin play roles in inflammation.
- Macrophages are key immune cells involved in regulating protease activity.
Purpose of the Study:
- To investigate the interaction of HNE and Eglin with macrophages.
- To determine if macrophages utilize oxidative bursts to inactivate these proteins.
Main Methods:
- Co-incubation of mouse peritoneal macrophages with HNE and Eglin.
- Assessment of inactivation using two methods: supernatant analysis and analysis of cell-associated molecules.
- Evaluation of the role of oxidative burst and free radicals in inactivation.
Main Results:
- Eglin did not induce radical production or bind to macrophages.
- Macrophages extensively inactivated both HNE and Eglin.
- Inactivation was mediated by stable, cell-derived molecules, likely proteases and inhibitors.
- Macrophage oxidative burst did not significantly affect the quantity of these inactivators.
Conclusions:
- Mouse peritoneal macrophages primarily use stable molecules, such as proteins, to restrict the activity of proteases and inhibitors.
- This mechanism is distinct from the potential use of free radicals and oxidants by other mononuclear phagocytes.