Macrophage elastases

One intensively investigated feature of the inflammatory process in COPD is the release of proteases from neutrophils and monocytic cells that destroy elastin and other components of the interstitial matrix (Table 1). The best studied protease is neutrophil elastase. Independent of its elastolytic activity, neutrophil elastase is a potent secretagogue. More recently matrix metalloproteases (MMP) have received increasing attention, in particular MMP 12 (macrophages elastase). To which extent and how exactly these proteases become activated is not clear at present. 

M. Senior, and S. D. Shapiro. Requirement for macrophage elastase for cigarette smoke-induced emphysema in mice. Science 1997 277(5334) 2002-2004. 

PMN Products - Neutral proteinases of PMN lysosomes degrade a wide variety of collective tissue substrates including elastin, proteoglycan, and collagen. Cathepsin G has been found only in PMN, and elastase from these cells has a substrate gpecificity different from that of pancreatic and macrophage elastase. In addition to their effects on connective tissue components, the neutral proteinases of PMN lysosomes also stimulate the activity of other cells involved in the inflammatory response. Both elastase and cathepsin G from human PMN stimulate the incor- poration of thymidine by human peripheral blood and splenic lymphocytes. The stimulated lymphocytes are of the B lineage, with no effect seen on T lymphocytes. 

The C-terminal domain of human macrophage elastase inhibited elastin degradation (Gronski jr. et al. 1996). 

IL-lra (17.5) Monocyte/macrophage, fibroblast Specifically inhibits IL-1 effects, including SIRS and sepsis in animal models and humans. Attenuation of coagulation, fibrinolytic, and complement systems, levels of PAF and neutrophil elastase. 

A number of factors increase the risk of disruption of the plaque the presence of a considerable amount of fat in the plaque the effects of physical stress on the vessel wall, particularly in the hypertensive patient and the activity of macrophages. Macrophages release proteases (e.g. colla-genase, elastase) which lead to breakdown of the plaque. Rupture of the plaque produces fissures that are sites for aggregation of platelets. Fragments from the rupture can occlude blood vessels. 

The secretion of protease, including collagenases and elastase, by activated intimal macrophages is necessary if the dense connective tissue matrix of a plaque is to be reduced. 

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