α 2 -Antiplasmin and plasminogen activator inhibitors in healing human skin wounds

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 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.

The Expression of Plasminogen Activator System in a Rat Model of Periodontal Wound Healing

“…15,16 Other studies have also found that the staining for PAI-2 increases with time after wounding and parallels the development of the cellular infiltrate. 17 During the stage of granulation tissue formation, fibroblasts, monocytes/macrophages, and endothelial cells appeared in the wound space. In the sections 854 from day 3 to 7 of periodontal wound healing, positive staining for u-PA, PAI-1, and PAI-2 was seen in the monocytes/macrophages and fibroblasts.…”

“…During this stage, the expression of PAI-1 and PAI-2 in the present study was similar to that found by others who have noted PAI-1 and PAI-2 expression by monocytes/macrophages and fibroblasts in developing granulation tissue. 11,17 Recent studies have shown the involvement of several components of the plasminogen-plasmin system in endothelial cell migration and angiogenesis. 1,8,11 In wound healing experiments in vitro, endothelial cells have been shown to upregulate u-PA, u-PAR, and PAI-1 expression.…”

Bio‐derived hydroxystearic acid ameliorates skin age spots and conspicuous pores

“…Increased alpha‐2‐antiplasmin may help to mitigate plasmin destruction of the DEJ and activation of MMPs . The increased levels of antithrombin III may be to balance the (pro)thrombin activity .…”

High tPA-expression in primary melanoma of the limb correlates with good prognosis

“…387, American Diagnostica, Greenwich CT, USA), PAI-1 (rabbit antibody, Department of Experimental and Chemical Endocrinology, University Medical Center St Radboud, Nijmegen, The Netherlands (Grebenschikov et al, 1997)), PAI-2 (goat antibody, Behring Werke AG, Marburg, Germany) and uPAR (rabbit antibody, Finsen Laboratory, Copenhagen, Denmark (Rønne et al, 1995)). To check sensitivity and specificity, stainings with other antibodies against tPA (rabbit polyclonal antibody, Department of Experimental and Chemical Endocrinology, University Medical Center St Radboud, Nijmegen, The Netherlands (Grebenschikov et al, 1997)), PAI-2 (goat polyclonal antibody, Institute for Immunology, University Hospital Heidelberg, Germany (Schaefer et al, 1996)) and uPAR (monoclonal antibody R2, Finsen Laboratory (Rønne et al, 1991)), and with two other antibodies against PAI-1 (monoclonal antibody Clone 1, Monozyme, Hoersholm, Denmark; monoclonal antibody no. 380, American Diagnostica) were compared on more than 100 lesions.…”