α2-Antiplasmin and plasminogen activator inhibitors in healing human skin wounds

• DOI: 10.1007/bf02505820
• Publication Date: 2006-10-11T02:48:42Z
• Authors: Birgit M. Schaefer; Katharina Maier; Ullrich Eickhoff; Michael Bechtel; Michael D. Kramer
• Keywords: Wound Healing; alpha-2-Antiplasmin; 0303 health sciences; Base Sequence; Transcription, Genetic; Molecular Sequence Data; Immunohistochemistry; Polymerase Chain Reaction; Plasminogen Inactivators; 03 medical and health sciences; Debridement; Molecular Probes; Plasminogen Activator Inhibitor 2; Humans; Wounds and Injuries; RNA, Messenger; Skin

Mechanical injury of tissues is followed by the formation of a provisional fibrin matrix, which is later replaced by granulation tissue. The fibrinolytic proteinase, plasmin, is thought to contribute to the displacement of the primary matrix. Plasmin is generated from the ubiquitous proenzyme plasminogen by plasminogen activators. The system of plasminogen activation is controlled at several levels: plasminogen activator inhibitors (PAI-1 and PAI-2) counteract the activity of plasminogen activators and alpha 2-antiplasmin inhibits the activity of plasmin. In order to elucidate the mechanisms that regulate the plasminogen activator system in healing human skin wounds, we performed the immunohistological study reported here. The plasmin inhibitor alpha 2-antiplasmin and PAI-2 were found in the primary fibrin-rich matrix and in the granulation tissue. alpha 2-Antiplasmin was diffusely distributed in the tissue and its distribution correlated with the presence and localization of plasmin(ogen) except that, in contrast to plasmin(ogen), the alpha 2-antiplasmin was apparently not cell-associated. The stainings for PAI-2 increased with time and paralleled the development of the cellular infiltrate. PAI-2 was found in association with cells, which were identified by double immunofluorescence stainings as monocytes/macrophages and fibroblasts. In line with the immunohistological data, 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 regulator of plasminogen activators, whereas alpha 2-antiplasmin may serve to control plasmin activity.