Modulation of macrophage activity by proteolytic enzymes. Differential regulation of IL-6 and reactive oxygen intermediates (ROIs) synthesis as a possible homeostatic mechanism in the control of inflammation.
Inflammatory foci are rich in proteases released by neutrophils (serine proteases) and macrophages (metalloproteases). These enzymes can degrade extracellular matrix proteins and cell membrane bound proteins thus contributing to the development and progression of inflammatory reaction. In this study we have investigated the influence of collagenase (metalloprotease) and trypsin (serine protease) on murine resident and oil-induced peritoneal macrophages (Mf). Short in vitro treatment of Mf, not affecting cell viability, significantly reduced the release of reactive oxygen intermediates (ROIs) and at the same time triggered the increase of IL-6 production and to lesser extent of TNF-alpha production. Both these effects were dependent on enzyme concentration used and were particularly well pronounced in resident macrophages. In addition both enzymes cleaved a number of cell-membrane molecules, including CD23, CD14, CD95L, and Mac-3. We hypothesize that the enzymatic digestion of certain Mf surface receptor proteins in inflammatory foci may be responsible for modification of cell behaviour either by preventing the generation of specific signal or alternatively by delivering a mock substitute signal to the cell interior. In effect inhibition of ROIs production limits their destructive effects and the increase in the secretion of IL-6 stimulates the synthesis of acute phase proteins and triggers other anti-inflammatory mechanisms thus directing Mf present in inflammatory foci into regulatory pathway rather than allowing them to perform solely the effector function.
Bryniarski
K
K
Department of Immunology, Medical College of Jagiellonian University, Cracow, Poland.
Maresz
K
K
Szczepanik
M
M
Ptak
M
M
Ptak
W
W
D000818:Animals; D002478:Cells, Cultured; D017364:Collagenases / Q000276:immunology; D010450:Endopeptidases / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology; D007249:Inflammation / Q000201:enzymology; D015850:Interleukin-6 / Q000096:biosynthesis*; D008264:Macrophages / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014357:Trypsin / Q000276:immunology
D015850:Interleukin-6; D017382:Reactive Oxygen Species; D010450:Endopeptidases; D014357:Trypsin; D017364:Collagenases