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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review


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Disease relevance of Acantholysis

  • Loss of epidermal cohesion in normal skin explants incubated with pemphigus foliaceous IgG was dependent upon the addition of plasminogen and was inhibited by aprotinin or lima bean trypsin inhibitor, which indicated that plasmin is the active enzyme in producing acantholysis [1].
  • Darier's disease (DD) is an autosomal dominantly inherited skin disorder characterized by loss of adhesion between epidermal cells (acantholysis) and abnormal keratinization [2].
  • Pemphigus vulgaris (PV) is an immune-mediated blistering skin disease characterized by acantholysis of the suprabasal epidermis and by IgG autoantibodies targeting a desmosomal component, desmoglein 3 [3].
  • Patterns of diffuse, mainly suprabasal acantholysis, with formation of bullae, were observed in the skin explants cultured with captopril or thiopronine at a 15-mM concentration after 5 days of culture; intraepidermal splits were present also at a 10-mM concentration [4].
  • Phosphatidylinositol-specific-phospholipase C cleaves urokinase plasminogen activator receptor from the cell surface and leads to inhibition of pemphigus-IgG-induced acantholysis in DJM-1 cells, a squamous cell carcinoma line [5].

High impact information on Acantholysis

  • These results indicate that at least one pathogenic epitope, which is sufficient to cause suprabasilar acantholysis in neonatal mice, is located on the amino-terminal region of PVA, an area thought to be important in cadherin homophilic adhesion [6].
  • In vitro studies indicate that Bos 6-specific IgG and, to a lesser extent, Bos 1-specific IgG can cause acantholysis [7].
  • Experimental treatments with caspase 3 or calpain inhibitors demonstrated that PV IgGs induced acantholysis through both pathways [8].
  • These observations suggest that PV IgG binding to dsg3 activates desmosomal signal transduction cascades leading to (i) p38MAPK and HSP27 phosphorylation and (ii) cytoskeletal reorganization, supporting a mechanistic role for signaling in PV IgG-induced acantholysis [9].
  • We demonstrated that only BALB/c mice immunized with a full-length Dsg 3 can produce pathogenic Abs capable of causing acantholysis of human foreskin in culture and blistering in neonatal mice [10].

Chemical compound and disease context of Acantholysis


Biological context of Acantholysis


Anatomical context of Acantholysis


Gene context of Acantholysis

  • In this study, we characterized the ultrastructural localization of in vivo-bound IgG, Dsg3, and desmoplakin during the process of acantholysis in an active mouse PV model, using post-embedding immunoelectron microscopy [20].
  • The relative decrease of Dsg3 (PVA) during epidermal differentiation might be responsible for the induction of suprabasal acantholysis in PV [24].
  • This internalization occurred prior to overt acantholysis, and was frequently associated with the induction of Dsg 2 expression in the basilar or lower layers of the epidermis [25].
  • Our results confirm the role of uPA in acantholysis and suggest an involvement of IL-1alpha/TNF-alpha in uPA induction [26].
  • To further examine the role of IL-1alpha, TNF-alpha and uPA in acantholysis, we performed antibody blocking studies [26].

Analytical, diagnostic and therapeutic context of Acantholysis


  1. Anti-cell surface pemphigus autoantibody stimulates plasminogen activator activity of human epidermal cells. A mechanism for the loss of epidermal cohesion and blister formation. Hashimoto, K., Shafran, K.M., Webber, P.S., Lazarus, G.S., Singer, K.H. J. Exp. Med. (1983) [Pubmed]
  2. Spectrum of novel ATP2A2 mutations in patients with Darier's disease. Sakuntabhai, A., Burge, S., Monk, S., Hovnanian, A. Hum. Mol. Genet. (1999) [Pubmed]
  3. Preferential activation of the complement system in the lower epidermis of patients with pemphigus vulgaris. Lapiere, J.C., Guitart, J., Ettlin, D.A., Chen, D.M., Amagai, M., Chan, L.S. Br. J. Dermatol. (1998) [Pubmed]
  4. In vitro acantholysis by captopril and thiopronine. Ruocco, V., de Angelis, E., Lombardi, M.L., Pisani, M. Dermatologica (1988) [Pubmed]
  5. Phosphatidylinositol-specific-phospholipase C cleaves urokinase plasminogen activator receptor from the cell surface and leads to inhibition of pemphigus-IgG-induced acantholysis in DJM-1 cells, a squamous cell carcinoma line. Asano, S., Seishima, M., Kitajima, Y. Clin. Exp. Dermatol. (2001) [Pubmed]
  6. Autoantibodies against the amino-terminal cadherin-like binding domain of pemphigus vulgaris antigen are pathogenic. Amagai, M., Karpati, S., Prussick, R., Klaus-Kovtun, V., Stanley, J.R. J. Clin. Invest. (1992) [Pubmed]
  7. Correlation of peptide specificity and IgG subclass with pathogenic and nonpathogenic autoantibodies in pemphigus vulgaris: a model for autoimmunity. Bhol, K., Natarajan, K., Nagarwalla, N., Mohimen, A., Aoki, V., Ahmed, A.R. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  8. Novel mechanisms of target cell death and survival and of therapeutic action of IVIg in Pemphigus. Arredondo, J., Chernyavsky, A.I., Karaouni, A., Grando, S.A. Am. J. Pathol. (2005) [Pubmed]
  9. Desmosome signaling. Inhibition of p38MAPK prevents pemphigus vulgaris IgG-induced cytoskeleton reorganization. Berkowitz, P., Hu, P., Liu, Z., Diaz, L.A., Enghild, J.J., Chua, M.P., Rubenstein, D.S. J. Biol. Chem. (2005) [Pubmed]
  10. BALB/c mice produce blister-causing antibodies upon immunization with a recombinant human desmoglein 3. Fan, J.L., Memar, O., McCormick, D.J., Prabhakar, B.S. J. Immunol. (1999) [Pubmed]
  11. Dexamethasone inhibits plasminogen activator activity in experimental pemphigus in vivo but does not block acantholysis. Anhalt, G.J., Patel, H.P., Labib, R.S., Diaz, L.A., Proud, D. J. Immunol. (1986) [Pubmed]
  12. Effects of steroid, retinoid, and protease inhibitors on the formation of acantholysis induced in organ culture of skins from patients with benign familial chronic pemphigus. Ikeda, S., Ogawa, H. J. Invest. Dermatol. (1991) [Pubmed]
  13. Methylprednisolone inhibits pemphigus acantholysis in skin cultures. Swanson, D.L., Dahl, M.V. J. Invest. Dermatol. (1983) [Pubmed]
  14. Differential coupling of M1 muscarinic and alpha7 nicotinic receptors to inhibition of pemphigus acantholysis. Chernyavsky, A.I., Arredondo, J., Piser, T., Karlsson, E., Grando, S.A. J. Biol. Chem. (2008) [Pubmed]
  15. Immunomorphologic and biochemical identification of the pemphigus foliaceous autoantigen within desmosomes. Rappersberger, K., Roos, N., Stanley, J.R. J. Invest. Dermatol. (1992) [Pubmed]
  16. Protease inhibitors prevent plasminogen-mediated, but not pemphigus vulgaris-induced, acantholysis in human epidermis. Schuh, T., Besch, R., Braungart, E., Flaig, M.J., Douwes, K., Sander, C.A., Magdolen, V., Probst, C., Wosikowski, K., Degitz, K. Biol. Chem. (2003) [Pubmed]
  17. A mouse model of pemphigus vulgaris by adoptive transfer of naive splenocytes from desmoglein 3 knockout mice. Aoki-Ota, M., Tsunoda, K., Ota, T., Iwasaki, T., Koyasu, S., Amagai, M., Nishikawa, T. Br. J. Dermatol. (2004) [Pubmed]
  18. Upregulation of P-cadherin expression in the lesional skin of pemphigus, Hailey-Hailey disease and Darier's disease. Hakuno, M., Akiyama, M., Shimizu, H., Wheelock, M.J., Nishikawa, T. J. Cutan. Pathol. (2001) [Pubmed]
  19. Erythema multiforme associated human autoantibodies against desmoplakin I and II: biochemical characterization and passive transfer studies into newborn mice. Foedinger, D., Elbe-Bürger, A., Sterniczky, B., Lackner, M., Horvat, R., Wolff, K., Rappersberger, K. J. Invest. Dermatol. (1998) [Pubmed]
  20. IgG binds to desmoglein 3 in desmosomes and causes a desmosomal split without keratin retraction in a pemphigus mouse model. Shimizu, A., Ishiko, A., Ota, T., Tsunoda, K., Amagai, M., Nishikawa, T. J. Invest. Dermatol. (2004) [Pubmed]
  21. UVB-induced acantholysis in endemic Pemphigus foliaceus (Fogo selvagem) and Pemphigus vulgaris. Reis, V.M., Toledo, R.P., Lopez, A., Diaz, L.A., Martins, J.E. J. Am. Acad. Dermatol. (2000) [Pubmed]
  22. Internalization of gap junctions in benign familial pemphigus (Hailey-Hailey disease) and keratosis follicularis (Darier's disease). Haftek, M., Kowalewski, C., Mesnil, M., Blaszczyk, M., Schmitt, D. Br. J. Dermatol. (1999) [Pubmed]
  23. In vitro acantholysis induced by D-penicillamine, captopril, and piroxicam on dead de-epidermized dermis. De Dobbeleer, G., Godfrine, S., Gourdain, J.M., De Graef, C., Heenen, M. J. Cutan. Pathol. (1992) [Pubmed]
  24. Differences in the expression of pemphigus antigens during epidermal differentiation. Iwatsuki, K., Harada, H., Yokote, R., Kaneko, F. Br. J. Dermatol. (1995) [Pubmed]
  25. Internalization of constitutive desmogleins with the subsequent induction of desmoglein 2 in pemphigus lesions. Iwatsuki, K., Han, G.W., Fukuti, R., Ohtsuka, M., Kikuchi, S., Akiba, H., Kaneko, F. Br. J. Dermatol. (1999) [Pubmed]
  26. Urokinase plasminogen activator mRNA is induced by IL-1alpha and TNF-alpha in in vitro acantholysis. Feliciani, C., Toto, P., Wang, B., Sauder, D.N., Amerio, P., Tulli, A. Exp. Dermatol. (2003) [Pubmed]
  27. Induction of keratinocyte IL-8 expression and secretion by IgG autoantibodies as a novel mechanism of epidermal neutrophil recruitment in a pemphigus variant. O'Toole, E.A., Mak, L.L., Guitart, J., Woodley, D.T., Hashimoto, T., Amagai, M., Chan, L.S. Clin. Exp. Immunol. (2000) [Pubmed]
  28. Fibronectin in pemphigus. Hunziker, T., Morgenthaler, J.J., Gerber, H.A. Dermatologica (1987) [Pubmed]
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