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

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Abstract

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 α2-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 α2-antiplasmin and PAI-2 were found in the primary fibrin-rich matrix and in the granulation tissue. α2-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 α2-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 α2-antiplasmin may serve to control plasmin activity.

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Authors and Affiliations

  1. Laboratorium für Immunpathologie, Institut für Immunologie der Universität Heidelberg, Im Neuenheimer Feld 305, D-69120, Heidelberg, Germany

    Birgit M. Schaefer, Michael Bechtel & Michael D. Kramer

  2. Pharmatec GmbH, Am Römerhof 35, D-60486, Frankfurt/Main, Germany

    Katharina Maier

  3. Chirurgische Abteilung, Sankt Josef Hospital Bochum, Gudrunstrasse 56, D-44791, Bochum, Germany

    Ullrich Eickhoff

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  1. Birgit M. Schaefer
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  2. Katharina Maier
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  3. Ullrich Eickhoff
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  4. Michael Bechtel
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  5. Michael D. Kramer
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Schaefer, B.M., Maier, K., Eickhoff, U. et al. α2-Antiplasmin and plasminogen activator inhibitors in healing human skin wounds. Arch Dermatol Res 288, 122–128 (1996). https://doi.org/10.1007/BF02505820

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  • DOI: https://doi.org/10.1007/BF02505820

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