Plasminogen activator inhibitor‐2 expression in inflamed appendix

Plasminogen activator inhibitors are thought to be responsible for the abolition of fibrinolytic activity in inflamed peritoneum. This reduction in the fibrin clearing capacity of the peritoneum promotes the formation of intraabdominal adhesions. High concentrations of plasminogen activator inhibitor‐2 (PAI‐2) have been previously found in inflamed peritoneal tissue using immunoassays, but it is undetectable in normal peritoneum. The aim of this study was to localize plasminogen activator inhibitor‐2 production in tissue by in situ mRNA hybridisation. Sections of normal and inflamed human appendix were hybridised with a digoxigenin labelled cDNA probe. In normal appendix staining was confined to macrophages in the mucosa. Macrophage staining was also seen in inflamed tissue but with a wider distribution throughout the appendix wall. PAI‐2 was also localized to mesothelial cells of inflamed but not normal appendix. Cell identities were confirmed using immunohistochemistry directed against cell specific markers. Staining was absent from control slides incubated with plasmid DNA or PAI‐2 probe following ribonuclease digestion. The identification of the cells expressing the PAI‐2 gene in peritoneum increases our understanding of the pathophysiological process leading to fibrin deposition within the abdomen during peritonitis.

[1]  J. Thompson,et al.  Plasminogen activator inhibitor 2 reduces peritoneal fibrinolytic activity in inflammation , 1993, The British journal of surgery.

[2]  K. Fleming,et al.  Localization of plasminogen activator inhibitor‐1 production in inflamed appendix by in situ mRNA hybridization , 1993, The Journal of pathology.

[3]  R. Lovell-Badge,et al.  Optimization of non‐isotopic in situ hybridization on formalin‐fixed, paraffin‐embedded material using digoxigenin‐labelled probes and transgenic tissues , 1992, The Journal of pathology.

[4]  J. Thompson,et al.  Peritoneal fibrinolytic activity and intra-abdominal adhesions , 1990, The Lancet.

[5]  T. Takeuchi,et al.  A Plasminogen Activator Inhibitor-2 from a Promyelocytic Leukemia Cell Line, PL-21, Binds to the Carboxy-Terminal Chain of Plasminogen Activators , 1990, Thrombosis and Haemostasis.

[6]  T. Kooistra,et al.  Characterization and fibrinolytic properties of human omental tissue mesothelial cells. Comparison with endothelial cells. , 1990, Blood.

[7]  T. Quertermous,et al.  Modulation of mRNA levels for urinary- and tissue-type plasminogen activator and plasminogen activator inhibitors 1 and 2 in human fibroblasts by interleukin 1. , 1989, Journal of immunology.

[8]  J. Thompson,et al.  Reduced human peritoneal plasminogen activating activity: Possible mechanism of adhesion formation , 1989, The British journal of surgery.

[9]  D. Loskutoff,et al.  Detection of both type 1 and type 2 plasminogen activator inhibitors in human cells , 1988, Journal of cellular physiology.

[10]  R. Medcalf,et al.  Plasminogen activator inhibitor 2: regulation of gene transcription during phorbol ester-mediated differentiation of U-937 human histiocytic lymphoma cells , 1987, Molecular and cellular biology.

[11]  D. Belin,et al.  Plasminogen activator-specific inhibitors in mouse macrophages: in vivo and in vitro modulation of their synthesis and secretion. , 1987, Journal of immunology.

[12]  R. Mattaliano,et al.  Purification and characterization of a plasminogen activator inhibitor from the histiocytic lymphoma cell line U-937. , 1986, The Journal of biological chemistry.

[13]  A. Vaheri,et al.  Urokinase‐type plasminogen activator and its inhibitor secreted by cultured human monocyte‐macrophages , 1985, Journal of cellular physiology.

[14]  H. Chapman,et al.  Macrophage fibrinolytic activity: Identification of two pathways of plasmin formation by intact cells and of a plasminogen activator inhibitor , 1982, Cell.

[15]  R. Buckman,et al.  A unifying pathogenetic mechanism in the etiology of intraperitoneal adhesions;. , 1976, The Journal of surgical research.

[16]  D. Silver,et al.  Serosal hypofibrinolysis. A cause of postoperative adhesions. , 1973, American journal of surgery.

[17]  J. Poole,et al.  Inhibitor of Fibrinolysis from Mesothelium , 1969, Nature.