Role of monocyte/macrophage derived matrix-metalloproteinases (gelatinases) in prolonged skin inflammation

Abstract 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 14 C-collagen fibrils, electrophoretic analysis of types I or IV collagen hydrolytic fragments and zymography. For 2–3 weeks, in parallel to mononuclear cell infiltratation, 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