Role of monocyte/macrophage derived matrix-metalloproteinases (gelatinases) in prolonged skin inflammation.
Neutral metalloproteinase activities in dermal extracellular space have been studied in several models of prolonged cutaneous inflammation in guinea pigs, by the following techniques: lysis of type I 14C-collagen fibrils, electrophoretic analysis of types I or IV collagen hydrolytic fragments and zymography. For 2-3 weeks, in parallel to mononuclear cell infiltration, collagenase activity was increased 3-4-fold. Constitutive gelatinases (67 and 72 kDa) augmented and larger molecular species emerged (92, 110 and 185 kDa), all of neutral metalloproteinase type. Guinea pig peritoneal monocytes/macrophages cultured with appropriate stimulation released large gelatinases in a similar set (92, 110, 210 kDa). These were purified from culture media by gelatin affinity and used in vivo as follows: (a) direct injection of monocyte/macrophage gelatinases; (b) injection of collagen I fragments (M(r) < 10,000) split off by gelatinases from preincubated (pH 5 and 38.5 degrees C) collagen I. In both instances, a mononuclear cell invasion of dermis occurred, indistinguishable from prolonged inflammation. These analogies suggest that monocyte/macrophage-derived metalloproteinases have an early and basic participation in the mechanism of prolonged inflammation.
Maillard
J L
JL
Laboratoire d'Enzymologie Moléculaire et Fonctionnelle, Institut Jacques Monod, Paris, France.
Favreau
C
C
Reboud-Ravaux
M
M
D000818:Animals; D002846:Chromatography, Affinity; D003094:Collagen / Q000302:isolation & purification / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D018093:Gelatinases / Q000302:isolation & purification / Q000378:metabolism*; D006168:Guinea Pigs; D007249:Inflammation / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D008264:Macrophages / Q000201:enzymology / Q000502:physiology*; D009000:Monocytes / Q000201:enzymology / Q000502:physiology*; D009169:Mycobacterium tuberculosis; D012867:Skin / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology*
D003094:Collagen; D018093:Gelatinases