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Expression of plasminogen activator inhibitor type 2 in normal and psoriatic epidermis

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Abstract

The plasminogen activator (PA) proteolytic cascade has been implicated in the regulation of cell activities, including proliferation and differentiation, both of which occur continuously in normal human epidermis and are aberrant in psoriatic epidermis. To elucidate further the mechanisms by which PA is regulated in epidermis, we evaluated the levels of PA inhibitors type 1 (PAI-1) and type 2 (PAI-2) in normal and psoriatic epidermis. PAI-2, but not PAI-1, was detectable by mRNA, antigen, and activity assays, indicating that PAI-2 is the predominant epidermal PA inhibitor. In situ hybridization revealed that PAI-2 mRNA occurred throughout normal epidermis, although the signal was most intense in the granular layers. Similarly, PAI-2 antigen was most prominent in the granular layers; its distribution in these differential layers was along the cell periphery. Diffuse, fainter staining for PAI-2 was also detected in the basal cells and in some spinous layers of normal epidermis. Extracts of normal epidermis contained PA inhibitory activity identified as PAI-2 by immunoprecipitation with specific antibody. In psoriatic epidermis, PAI-2 mRNA and antigen were most prominent in the more superficial layers beneath the cornified cells. As with normal epidermis, PAI-2 assumed a pericellular distribution in the psoriatic cells. These data demonstrate that PAI-2 is constitutively expressed in vivo by keratinocytes in human epidermis and indicate that this protein is the predominant inhibitor of PA activity in normal and psoriatic human epidermis.

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References

  • Andreasen PA, Nielsen LS, Kristensen P, Grøndahl-Hansen J, Skriver L, Danø K (1985) Plasminogen activator inhibitor from human fibrosarcoma cells binds urokinase-type plasminogen activator but not its proenzyme. J Biol Chem 261:7644–7651

    Google Scholar 

  • Andreasen PA, Georg B, Lund LR, Riccio A, Stacey SN (1990) Plasminogen activator inhibitors: hormonally regulated serpins. Mol Cell Endocrinol 68:1–19

    Google Scholar 

  • Antalis TM, Dickinson JL (1992) Control of plasminogen-activator inhibitor type 2 gene expression in the differentiation of monocytic cells. Eur J Biochem 205:203–209

    Google Scholar 

  • Arndt AD, Gohill J, Rankin K, Houwen B, Hart DA (1989) Differentiation-linked expression of the plasminogen activator inhibitor type-2 gene in the human HL-60 promyelocytic cell line. Exp Cell Res 185:473–481

    Google Scholar 

  • Astedt B, Haegerstrand I, Lecander I (1986) Cellular localization in placenta of placental type plasminogen activator inhibitor. Thromb Haemost 56:63–65

    Google Scholar 

  • Baird J, Lazarus GS, Belin D, Vassalli J-D, Busso N, Gubler P, Jensen PJ (1990) mRNA for tissue type plasminogen activator is present in lesional epidermis from patients with psoriasis, pemphigus, or bullous pemphigoid, but is not detected in normal epidermis. J Invest Dermatol 95:548–552

    Google Scholar 

  • Christensen U, Holmberg L, Bladh B, Astedt B (1982) Kinetics of the reaction between urokinase and an inhibitor of fibrinolysis from placental tissue. Thromb Haemost 55:8–11

    Google Scholar 

  • Danø K, Andreasen PA, Grøndahl-Hansen J, Kristensen P, Nielsen LS, Skriver L (1985) Plasminogen activators, tissue degradation and cancer. Adv Cancer Res 44:139–266

    Google Scholar 

  • Ericksen J, Kristensen P, Pyke C, Danø K (1989) Plasminogen activator inhibitor (type-1) in rat adrenal medulla. Histochemistry 92:377–383

    Google Scholar 

  • Erickson LA, Ginsberg MH, Loskutoff DJ (1984) Detection and partial characterization of an inhibitior of plasminogen activator in human plateles. J Clin Invest 74:1465–1472

    Google Scholar 

  • Erickson LA, Flci GJ, Lund JE, Boyle TP, Polites HG, Marotti KR (1990) Development of venous occlusions in mice transgenic for the plasminogen activator inhibitor 1 gene. Nature 346:74–76

    Google Scholar 

  • Fay WP, Shapiro AD, Shih JL, Schleef RR, Ginsburg D (1992) Complete deficiency of plasminogen activator inhibitor 1 due to a frameshift mutation. N Engl J Med 327:1729–1733

    Google Scholar 

  • Fraki JE, Hopsu-Havu VK (1972) Differential extraction of protease and of endogenous protease inhibitors. Arch Derm Forsch 242:329–342

    Google Scholar 

  • Fuchs E (1990) Epidermal differentiation: the bare essentials. J Cell Biol 111:2807–2814

    Google Scholar 

  • Genton C, Kruithof EKO, Schleuning W-D (1987) Phorbol ester induces the biosynthesis of glycosylated and nonglycosylated plasminogen activator inhibitor 2 in high excess over urokinase-type plasminogen activator in human U-937 lymphoma cells. J Cell Biol 104:705–712

    Google Scholar 

  • Grøndahl-Hansen J, Nielsen LS, Kristensen P, Grøndahl-Hansen V, Andreasen PA, Danø K (1985) Plasminogen activator in psoriatic scales is of the tissue type PA as identified by monoclonal antibodies. Br J Dermatol 133:257–263

    Google Scholar 

  • Grøndahl-Hansen J, Ralfkiaer E, Nielsen LS, Kristensen P, Frentz G, Danø K (1987) Immuohistochemical localization of urokinase- and tissue-type plasminogen activators in psoriatic skin. J Invest Dermatol 88:28–32

    Google Scholar 

  • Hashimoto K, Katayama I, Nishioka K (1985) Tissue plasminogen activator inhibitor in the epidermis. Br J Dermatol 113:523–527

    Google Scholar 

  • Hashimoto K, Wun TC, Baird J, Lazarus GS, Jensen PJ (1989) Characterization of keratinocyte plasminogen activator inhibitors and demonstration of the prevention of pemphigus IgG-induced acantholysis by a purified plasminogen activator inhibitor. J Invest Dermatol 92:301–315

    Google Scholar 

  • Hekman CM, Loskutoff DJ (1985) Endothelial cells produce a latent inhibitor of plasminogen activators that can be activated by denaturants. J Biol Chem 260:11581–11587

    Google Scholar 

  • Hekman CM, Lsokutoff DJ (1987) Fibrinolytic pathways and the endothelium. Semin Thromb Hemost 13:514–527

    Google Scholar 

  • Hibino T, Izaki S, Ohkuma M, Kon S, Thorsen S, Astedt B (1988) Epidermal plasminogen activator inhibitor (PAI) is immunologically identical to placental-type PAI-2. FEBS Lett 231:202–206

    Google Scholar 

  • Isseroff RR, Rifkin DB (1983) Plasminogen is present in the basal layer of the epidermis. J Invest Dermatol 80:297–299

    Google Scholar 

  • Jensen PJ, Baird J, Morioka S, Lessin S, Lazarus GS (1988) Epidermal plasminogen activator is abnormal in cutaneous lesions. J Invest Dermatol 90:777–782

    Google Scholar 

  • Joslin G, Griffin GI, August AM, Adams S, Fallon RJ, Senior RM, Perlmutter DH (1992) The serpin-enzyme complex receptor mediates the neutrophil chemotactic effect of alpha-1-antitrypsin-elastase complexes and amyloid-β peptide. J Clin Invest 90:1150–1154

    Google Scholar 

  • Keeton M, Eguchi Y, Sawdey M, Ahn C, Loskutoff DJ (1993) Cellular localization of type 1 plasminogen activator inhibitor messenger RNA and protein in murine renal tissue. Am J Pathol 142:59–70

    Google Scholar 

  • Kilpatrick L, Johnson JL, Nickbarg EB, Wang ZM, Clifford TF, Banach M, Cooperman BS, Douglas SD, Rubin H (1991) Inhibition of human neutrophil superoxide generation by alpha-1-antichymotrypsin. J Immunol 146:2388–2393

    Google Scholar 

  • Kopitar M, Rozman B, Babnik J, Turk V, Mullins DE, Wun T-C (1985) Human leukocyte urokinase inhibitor: purification, characterization, and comparative studies against different plasminogen activators. Thromb Haemost 54:750–755

    Google Scholar 

  • Kruithof EKO (1988) Inhibitors of plasminogen activators. In: Kluft C (ed) Tissue-type plasminogen activator, physiological and clinical aspects. CRC Press, Boca Raton, Fl, pp 189–209

    Google Scholar 

  • Kruithof EKO, Vassalli J-D, Schleuning W-D, Mattaliano RJ, Bachmann F (1986) Purification and characterization of a plasminogen activator inhibitor from the histiocytic lymphoma cell line U-937. J Biol Chem 261:11207–11213

    Google Scholar 

  • Kumar S, Baglioni C (1991) Protection from tumor necrosis factor-mediated cytolysis by overexpression of plasminogen activator inhibitor type 2. J Biol Chem 266:20960–20964

    Google Scholar 

  • Lavker RM, Miller S, Wilson C, Cotsarelis G, Wei Z-G, Yang J-S, Sun T-T (1993) Hair follicle stem cells: their location, role in hair cycle, and involvement in skin tumor formation. J Invest Dermatol 101:165–265

    Google Scholar 

  • Lecander I, Astedt B (1986) Isolation of a new specific plasminogen activator inhibitor from pregnancy plasma. Br J Haematol 62:221–228

    Google Scholar 

  • Levin EG (1986) Quantitation and properties of the active and latent plasminogen activator inhibitors in cultures of human endothelial cells. Blood 67:1309–1313

    Google Scholar 

  • Loscalzo J, Braunwald E (1988) Tissue plasminogen activator. N Engl J Med 319:925–931

    Google Scholar 

  • Lucore CL, Fujii S, Wun T-C, Sobel BE, Billadello JJ (1988) Regulation of the expression of type 1 plasminogen activator inhibitor in HepG2 cells by epidermal growth factor. J Biol Chem 263:15845–15848

    Google Scholar 

  • Lyons-Giordano B, Jensen PJ, Spiers EM, Lazarus GS (1993) Differential expression of plasminogen activator enzymes in normal and psoriatic epidermis. In: Dubertret L (ed) Psoriasis. ISED Publishing Co. (in press)

  • Mansbridge JN, Knapp AM, Strefling AM (1984) Evidence for an alternative pathway of keratinocyte maturation in psoriasis from an antigen found in psoriatic but not normal epidermis. J Invest Dermatol 83:296–301

    Google Scholar 

  • Mansbridge JN, Knapp AM (1987) Changes in keratinocyte maturation during wound healing. J Invest Dermatol 89:253–263

    Google Scholar 

  • Nishioka K, Ryan TJ (1971) Inhibitors and proactivators of fibrinolysis in human epidermis. Br J Dermatol 85:561–565

    Google Scholar 

  • Philips M, Juul A-G, Thorsen S, Selmer J, Zeuthen J (1986) Immunological relationship between the fast-acting plasminogen activator inhibitors from plasma, blood plateles, and endothelial cells demonstrated with a monoclonal antibody against an inhibitor from placenta. Thromb Haemost 55:213–217

    Google Scholar 

  • Pollanen J, Stephens RW, Vaheri A (1991) Directed plasminogen activation at the surface of normal and malignant cells. Adv Cancer Res 57:273–328

    Google Scholar 

  • Rao JS, Chen M, Festoff BW (1993) Plasminogen activator inhibitor 1, the primary regulator of fibrinolysis, in normal human cerebrospinal fluid. J Neurosci Res 34:340–345

    Google Scholar 

  • Remold-O'Donnell E (1993) The ovalbumin family of serpin proteins. FEBS 315:105–108

    Google Scholar 

  • Rømer J, Lund ER, Ericksen J, Ralfkiaer E, Zeheb R, Gelehrter TD, Danø K, Kristensen P (1991) Differential expression of urokinase-type plasminogen activator and its type-1 inhibitor during healing of mouse skin wounds. J Invest Dermatol 97:803–811

    Google Scholar 

  • Sappino A-P, Belin D, Huarte J, Hirschel-Scholz S, Saurat J-H, Vassalti J-D (1991) Differential protease expression by cutaneous squamous and basal cell carcinomas. J Clin Invest 88:1073–1079

    Google Scholar 

  • Schleuning W-D, Medcalf RL, Hession C, Rothenbuhler R, Shaw A, Kruithof EKO (1987) Plasminogen activator inhibitor 2: regulation of gene transcription during phorbol ester mediated differentiation of U-937 human histiocytic lymphoma cells. Mol Cell Biol 7:4564–4567

    Google Scholar 

  • Schneiderman J, Sawdey MS, Keeton MR, Borden GR, Bernstein EF, Dilley RB, Loskutoff DJ (1992) Increased type 1 plasminogen activator inhibitor gene expression in atherosclerotic human arteries. Proc Natl Acad Sci USA 89:6998–7002

    Google Scholar 

  • Schwartz BS, Bradshaw JD (1992) Regulation of plasminogen activator inhibitor mRNA levels in lipopolysaccharide-stimulated human monocytes. J Biol Chem 267:7089–7094

    Google Scholar 

  • Sprengers ED, Kluft C (1987) Plasminogen activator inhibitors. Blood 69:381–387

    Google Scholar 

  • Strickland S, Beers WH (1976) Studies on the role of plasminogen activator in ovulation. J Biol Chem 252:5694–5702

    Google Scholar 

  • Vassalli J-D, Sappino A-P, Belin D (1991) The plasminogen activator/plasmin system. J Clin Invest 88:1067–1071

    Google Scholar 

  • van Mourik JA, Lawrence DA, Loskutoff DJ (1984) Purification of an inhibitor of plasminogen activation (antiactivator) synthesized by endothelial cells. J Biol Chem 259:14914–14921

    Google Scholar 

  • Wun T-C, Reich E (1987) An inhibitor of plasminogen activation from human placenta. J Biol Chem 262:3646–3653

    Google Scholar 

  • Wohlwend A, Belin D, Vassalli J-D (1987) Plasminogen activatorspecific inhibitors produced by human monocytes/macrophages. J Exp Med 165:320–339

    Google Scholar 

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Authors and Affiliations

  1. Department of Dematology, University of Pennsylvania, 242 CRB, 422 Curie Boulevard, 19104-6142, Philadelphia, PA, USA

    B. Lyons-Giordano, C.-S. Chen, G. Lazarus & P. J. Jensen

  2. Scripps Clinic and Research Foundation, 10666 North Torrey Pines Road, 92037, La Jolla, CA, USA

    D. Loskutoff & M. Keeton

Authors
  1. B. Lyons-Giordano
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  2. C.-S. Chen
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  3. G. Lazarus
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  4. P. J. Jensen
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  5. D. Loskutoff
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  6. M. Keeton
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Lyons-Giordano, B., Chen, CS., Lazarus, G. et al. Expression of plasminogen activator inhibitor type 2 in normal and psoriatic epidermis. Histochemistry 101, 105–112 (1994). https://doi.org/10.1007/BF00269356

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  • DOI: https://doi.org/10.1007/BF00269356

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