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Thromb Haemost 1998; 79(04): 813-817
DOI: 10.1055/s-0037-1615070
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The Distribution of the Secreted and Intracellular Forms of Plasminogen Activator Inhibitor 2 (PAI-2) in Human Peripheral Blood Monocytes Is Modulated by Serum

Helen Ritchie
1   From the Department of Molecular and Cell Biology, University of Aberdeen, Aberdeen, Scotland, UK
,
Nuala A. Booth
1   From the Department of Molecular and Cell Biology, University of Aberdeen, Aberdeen, Scotland, UK
› Author Affiliations
Further Information

Publication History

Received 20 May 1997

Accepted after resubmission 03 December 1997

Publication Date:
07 December 2017 (online)

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Summary

Plasminogen activator inhibitor 2 (PAI-2) is produced by activated monocytes in two forms, intracellular and secreted. We have studied the distribution of these two forms in unstimulated human peripheral blood monocytes and after stimulation by thrombin. Fetal calf serum (FCS) in the culture medium was absolutely necessary for accumulation of intracellular PAI-2; but not for synthesis and secretion. Even at a concentration as low as 0.1%, FCS restored accumulation of intra-cellular PAI-2. Increasing concentrations of FCS resulted in an increase in the ratio of intracellular to secreted PAI-2. The factor that promoted accumulation of intracellular PAI-2 was not a platelet product. Failure of monocytes to accumulate PAI-2 did not reflect leakage due to cell death, as assessed by LDH in culture supernatants. We propose that accumulation of intracellular PAI-2 is not simply due to poor secretion, but is an active process that is modulated by factor(s) found in serum.

 

  • References

  • 1 Kruithof EKO, Baker MS, Bunn CL. Biological and clinical aspects of plasminogen activator inhibitor type 2. Blood 1995; 86: 4007-24.
    PubMedSearch in Google Scholar
  • 2 Booth NA. Natural inhibitors of fibrinolysis. In: Haemostasis and thrombosis. Bloom AL, Forbes CD, Thomas TP, Tuddenham EGD. eds. 3rd ed. Churchill Livingstone; 1994. pp 699-715.
    Search in Google Scholar
  • 3 Whawell SA, Vipond MN, Scott-Coombes Thompson JN. Plasminogen activator inhibitor 2 reduces peritoneal activity in inflammation. Br J Surg 1993; 80: 107-11.
    CrossrefPubMedSearch in Google Scholar
  • 4 Lyons-Giordano B, Loskutoff D, Chen C-S, Lazarus G, Keeton M, Jensen PJ. Expression of plasminogen activator inhibitor type 2 in normal and psoriatic epidermis. Histochem 1994; 101: 105-12.
    CrossrefPubMedSearch in Google Scholar
  • 5 Mueller BM, Yu UB, Laug WE. Overexpression of plasminogen activator inhibitor 2 in human melanoma cells inhibits spontaneous metastasis in scid/scid mice. Proc Natl Acad Sci USA 1995; 92: 205-9.
    CrossrefPubMedSearch in Google Scholar
  • 6 Remold O’Donnell E. The ovalbumin family of serpin proteins. FEBS Lett 1993; 315: 105-9.
    CrossrefPubMedSearch in Google Scholar
  • 7 Coughlin P, Sun J, Cerruti L, Salem HH, Bird P. Cloning and molecular characterization of an intracellular serine proteinase inhibitor. J Biol Chem 1993; 90: 9417-21.
    PubMedSearch in Google Scholar
  • 8 Morgernstern KA, Henzel WJ, Baker JB, Wong S, Pastuszyn A. Isolation and characterization of an intracellular serine proteinase inhibitor from a monkey kidney epithelial cell line. J Biol Chem 1992; 268: 21560-8.
    PubMedSearch in Google Scholar
  • 9 Riewald M, Schleef RR. Molecular cloning of bomapin (protease inhibitor 10), a novel human serpin that is expressed specifically in the bone marrow. J Biol Chem 1995; 270: 26754-60.
    CrossrefPubMedSearch in Google Scholar
  • 10 Schwartz BS, Monroe MC, Levin EG. Increased release of plasminogen activator inhibitor type 2 accompanies the human mononuclear cell tissue factor response to lipopolysaccharide. Blood 1988; 71: 734-41.
    PubMedSearch in Google Scholar
  • 11 Medcalf RL, Kruithof EKO, Schleuning W-D. Plasminogen activator inhibitor 1 and 2 are tumor necrosis factor/cachetin-responsive genes. J Exp Med 1988; 168: 751-9.
    CrossrefPubMedSearch in Google Scholar
  • 12 Genton C, Kruithof EKO, Schleuning W-D. Phorbol ester induces the biosynthesis of glycosylated and non-glycosylated plasminogen activator inhibitor 2 in high excess over urokinase-type plasminogen activator in human U937 lymphoma cells. J Cell Biol 1987; 104: 705-12.
    CrossrefPubMedSearch in Google Scholar
  • 13 Ritchie HM, Jamieson A, Booth NA. Thrombin modulates synthesis of plasminogen activator inhibitor 2 by human peripheral blood monocytes. Blood 1995; 86: 3428-35.
    PubMedSearch in Google Scholar
  • 14 Ritchie HM, Jamieson A, Booth NA. Peripheral blood monocyte synthesis of plasminogen activator inhibitor 2 in response to native and modified LDL. Thromb Haemost 1995; 74: 1521-7.
    Thieme ConnectPubMedSearch in Google Scholar
  • 15 Pytel BA, Peppel K, Baglioni C. Plasminogen activator inhibitor type-2 is a major protein induced in human fibroblasts and SK-MEL-109 melanoma cells by tumor necrosis factor. J Cell Physiol 1990; 144: 416-22.
    CrossrefPubMedSearch in Google Scholar
  • 16 Von Heijne G, Liljestrom P, Mikus P, Andersson H, Ny T. The efficiency of the uncleaved secretion signal in the plasminogen activator inhibitor type 2 protein can be enhanced by point mutations that increase its hydro-phobicity. J Biol Chem 1991; 266: 15240-4.
    PubMedSearch in Google Scholar
  • 17 Mikus P, Ny T. Intracellular polymerization of the serpin plasminogen activator inhibitor type 2. J Biol Chem 1995; 271: 10048-54.
    PubMedSearch in Google Scholar
  • 18 Steven J, Cottingham IR, Chinery SA, Goodey AR, Courtney M, Ballance DJ. Purification and characterization of plasminogen activator inhibitor 2 produced in Saccharomyces cerevisiae . Eur J Biochem 1991; 196: 431-7.
    CrossrefPubMedSearch in Google Scholar
  • 19 MacGregor IR, Booth NA. An enzyme-linked immunosorbent assay to study the cellular secretion of endothelial plasminogen activator inhibitor (PAI-1). Thromb Haemost 1988; 58: 68-72.
    PubMedSearch in Google Scholar
  • 20 Sudlow AW, Carey F, Forder R, Rothwell NJ. The role of lipocortin-1 in dexamethasone-induced suppression of PGE2 and TNFα release from human peripheral blood monocytes. Br J Pharmacol 1995; 117: 1449-55.
    PubMedSearch in Google Scholar
  • 21 Erickson LA, Rushford CL, Dolney DJ, Wilson GN, Schmickel RD. Structure and variation of human ribosomal DNA: molecular analysis of cloned fragments. Gene 1991; 16: 1-9.
    PubMedSearch in Google Scholar
  • 22 Jensen PJ, Wu Q, Janowitz P, Ando Y, Schechter NM. Plasminogen activator inhibitor type 2: an intracellular keratinocyte differentiation product that is incorporated into the cornified envelope. Exp Cell Res 1995; 217: 65-72.
    CrossrefPubMedSearch in Google Scholar
  • 23 Ogura M, Morishima Y, Ono R, Kato Y, Hirabayashi M, Nagura H, Saito H. Establishment of a novel human megakaryoblastic leukemia cell line, MEG-01, with positive Philadelphia chromosome. Blood 1985; 66: 1384-92.
    PubMedSearch in Google Scholar
  • 24 Belin D, Bost S, Vassalli J-D, Strub K. A two-step recognition of signal sequences determines the translocation efficiency of proteins. EMBO J 1996; 15: 468-75.
    PubMedSearch in Google Scholar
  • 25 Ritchie H, Booth NA. PAI-2 is secreted by monocytes via an ER-Golgi independent mechanism. Thromb Haemost. 1997 Suppl p579, abstract SC 2365.
    PubMedSearch in Google Scholar
  • 26 Rubartelli A, Cozzolino F, Talio M, Sitia M. A novel secretory pathway for interleukin-1b, a protein lacking a signal sequence. EMBO J 1990; 9: 1503-10.
    PubMedSearch in Google Scholar
  • 27 Ritchie H, Jamieson A, Booth NA. Regulation, location and activity of plasminogen activator inhibitor 2 (PAI-2) in peripheral blood monocytes, macrophages and foam cells. Thromb Haemost 1997; 77: 1168-73.
    Thieme ConnectPubMedSearch in Google Scholar
  • 28 Gan H, Newman GW, Remold HG. Plasminogen activator inhibitor type 2 prevents programmed cell death of human macrophages infected with Mycobacterium avium . J Immunol 1995; 155: 1304-9.
    PubMedSearch in Google Scholar
  • 29 Dickinson JL, Antalis TM. Tissue factor and plasminogen activator inhibitor expression in the differentiation of myeloid leukemic cells. Leukemia 1993; 7: 864-70.
    PubMedSearch in Google Scholar
  • 30 Kumar S, Baglioni C. Protection from tumor necrosis factor-mediated cytolysis by overexpression of plasminogen activator inhibitor type-2. J Biol Chem 1991; 266: 20960-6.
    PubMedSearch in Google Scholar
  • 31 Dickinson JL, Bates EJ, Ferrante A, Antalis T. Plasminogen activator inhibitor type 2 inhibits tumor necrosis factor α-induced apoptosis. J Biol Chem 1995; 270: 27894-900.
    CrossrefPubMedSearch in Google Scholar
  • 32 Ray CA, Black RA, Kronheim GR, Greenstreet TA, Sleath PR, Salvasen GS, Pickup DJ. Viral inhibition of inflammation: cowpox virus encodes an inhibitor of the interleukin-1β converting enzyme. Cell 1991; 597-605.
    PubMedSearch in Google Scholar