Summary
Addition of human plasminogen to three different pemphigus plasma samples showed a synergistic effect on acantholysis in the skin organ culture model. Human plasmin itself, without addition of pemphigus plasma, induced typical acantholytic changes in the skin explants, causing different types of acantholysis in a dose- and time-dependent manner: in the presence of 3 CU plasmin per ml culture medium, focal suprabasilar acantholysis of pemphigus vulgaris type could be detected after 72 h incubation, whereas 15 CU/ml caused extended acantholysis of pemphigus foliaceus type in the upper epidermal layers after 24 h, and extended acantholysis of benign chronic pemphigus (Hailey-Hailey disease) type comprising all layers of the epidermis after 48 h incubation. Plasminogen activator levels (Mr 55,000 urokinase type) in tissue extracts of skin explants and in culture media were reduced after 24 and 48 h incubation with pemphigus IgG as compared to control experiments with normal human igG; this probably resulted from urokinase inactivation by reaction with inhibitors. These results lend support to the hypothesis proposed by Hashimoto et al. in 1983 that the plasminogen activator-plasmin system could play an essential role in the protease mechanisms of pemphigus acantholysis.
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References
Ahmed AR (1984) Diagnosis of bullous disease and studies in the pathogenesis of blister formation using immunopathological techniques. J Cutan Pathol 11:237–248
Anhalt GJ, Patel HP, Labib RS, Diaz LA, Proud D (1986) Dexamethasone inhibits plasminogen activator activity in experimental pemphigus in vivo but does not block acantholysis. J Immunol 136:113–117
Avalos E, Patel H, Anhalt GJ, Diaz LA (1984) Autoimmune injury of squamous epithelium by pemphigus autoantibodies. Br J Dermatol 111:359–365
Birkedal-Hansen H, Taylor RE (1983) Production of three plasminogen activators and an inhibitor in keratinocyte cultures. Biochim Biophys Acta 756:308–318
Farb RM, Dykes R, Lazarus GS (1978) Anti-epidermal-cell-surface pemphigus antibody detaches viable epidermal cells from culture plates by activation of proteinase. Proc Natl Acad Sci USA 75:459–463
Gaffney PJ, Philo RD (1981) A commentary on new methodology in haemostasis using chromogenic substrates. In: Fareed J, Messmore HL, Fenton II JW, Brinkhous KM (eds) Perspectives in haemostasis. Pergamon Press, New York, pp 405–417
Hashimoto K, Shafran KM, Webber PS, Lazarus GS, Singer KH (1983) Anti-cell surface pemphigus autoantibody stimulates plasminogen activator activity of human epidermal cells. J Exp Med 157:259–272
Hunziker T, Nydegger UE, Spaeth PJ, Gerber HA, Hess M, Wiesmann U, Krebs A (1985) High doses of antigennonspecific IgG do not inhibit pemphigus acantholysis in skin organ cultures. Arch Dermatol Res 277:299–303
Hunziker T, Nydegger UE, Lerch PG, Vassalli J-D (1986) Platelet-derived factors enhance pemphigus acantholysis in skin organ cultures. Clin Exp Immunol 64:442–449
Ichinose A, Fujikawa K, Suyama T (1986) The activation of pro-urokinase by plasma kallikrein and its inactivation by thrombin. J Biol Chem 261:3486–3489
Isseroff RR, Rifkin DB (1983) Plasminogen is present in the basal layer of the epidermis. J Invest Dermatol 80:297–299
Levin EG (1983) Latent tissue plasminogen activator produced by human endothelial cells in culture: evidence for an enzyme-inhibitor complex. Proc Natl Acad Sci USA 80:6804–6808
Philips M, Juul A-G, Thorsen S (1984) Human endothelial cells produce a plasminogen activator inhibitor and a tissuetype plasminogen activator-inhibitor complex. Biochim Biophys Acta 802:99–110
Rickli EE, Cuendet PA (1971) Isolation of plasmin-free human plasminogen with N-terminal glutamic acid. Biochim Biophys Acta 250:447–451
Sarkany I, Grice K, Caron GA (1965) Organ culture of adult human skin. Br J Dermatol 77:65–76
Singer KH, Hashimoto K, Jensen PJ, Morioka S, Lazarus GS (1985) Pathogenesis of autoimmunity in pemphigus. Ann Rev Immunol 3:87–108
Skerrow CJ (1985) Plasmin induces pemphigus-type acantholysis in normal human skin. Br J Dermatol 113:765 (abstract)
Skriver L, Nielsen LS, Stephens R, Dano K (1982) Plasminogen activator released as inactive proenzyme from murine cells transformed by sarcoma virus. Eur J Biochem 124:409–414
Stanley JR, Koulu L, Thivolet C (1984) Distinction between epidermal antigens binding pemphigus vulgaris and pemphigus foliaceus autoantibodies. J Clin Invest 74:313–320
Vassalli J-D, Dayer J-M, Wohlwend A, Belin D (1984) Concomitant secretion of prourokinase and of a plasminogen activator-specific inhibitor by cultured human monocytes-macrophages. J Exp Med 159:1653–1668
Wun TC, Ossowski L, Reich E (1982) A proenzyme form of human urokinase. J Biol Chem 257:7262–7268
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Hunziker, T., Vassalli, J.D. Plasmin induces acantholysis in skin organ cultures. Arch Dermatol Res 279, 341–346 (1987). https://doi.org/10.1007/BF00431228
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DOI: https://doi.org/10.1007/BF00431228