ALPHA(2)-ANTIPLASMIN AND PLASMINOGEN-ACTIVATOR INHIBITORS IN HEALING HUMAN SKIN WOUNDS

Mechanical injury of tissues is followed by the formation of a provisi onal fibrin matrix, which is later replaced by granulation tissue, The fibrinolytic proteinase, plasmin, is thought to contribute to the dis placement of the primary matrix, Plasmin is generated from the ubiquit ous proenzyme plasminogen by plasminogen activators, The system of pla sminogen activation is controlled at several levels: plasminogen activ ator inhibitors (PAI-1 and PAI-2) counteract the activity of plasminog en activators and alpha(2)-antiplasmin inhibits the activity of plasmi n, In order to elucidate the mechanisms that regulate the plasminogen activator system in healing human skin wounds, we performed the immuno histological study reported here, The plasmin inhibitor alpha(2)-antip lasmin and PAI-2 were found in the primary fibrin-rich matrix and in t he granulation tissue, alpha(2)-Antiplasmin was diffusely distributed in the tissue and its distribution correlated with the presence and lo calization of plasmin(ogen) except that, in contrast to plasmin(ogen), the alpha(2)-antiplasmin was apparently not cell-associated. The stai nings for PAI-2 increased with time and paralleled the development of the cellular infiltrate, PAI-2 was found in association with cells, wh ich were identified by double immunofluorescence stainings as monocyte s/macrophages and fibroblasts, In line with the immunohistological dat a, polymerase chain reaction after reverse transcription revealed mRNA for PAI-2 in healing human skin wounds, Taken together, our findings indicate that in healing human skin wounds, PAI-2 is the primary regul ator of plasminogen activators, whereas alpha(2)-antiplasmin may serve to control plasmin activity.