eISSN: 1644-4124
ISSN: 1426-3912
Central European Journal of Immunology
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3-4/2004
vol. 29
 
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abstract:

Review paper
The role of adamalysins (ADAMs) in destruction of anchoring fibers involved in pathogenesis of selected subepidermal bullous diseases

Agnieszka Żebrowska
,
Elżbieta Waszczykowska
,
Ewa Joss-Wichman

Centr Eur J Immunol 2004; 29 (3-4): 85-89
Online publish date: 2006/02/06
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Pathogenesis of autoimmune subepidermal bullous diseases, which include pemphigoid (BP) and dermatitis herpetiformis (DH), is associated with destruction of basement membrane components, leading to formation of bullous lesions. Antibodies binding to autoantigens localized in the basement membrane activate a series of immunological and enzymatic phenomena that lead to destruction of anchoring fibers. Recent data reveal the important role of certain enzymes, metalloproteinases: collagenases, stromelysins and gelatinases, as well as their tissue inhibitors in skin lesions in destruction of the basement membrane and formation of blisters. There is also evidence that adamalysins (ADAMs – a disintegrin and metalloproteinases), enzymes combining features of both adhesion molecules and proteases, may be involved in this process. Recent data and results of own preliminary studies, concerning biochemical properties of these enzymes and their high affinity to components of the basement membrane, especially collagen XVII and VII, are presented in the paper. Disturbed expression of adamalysins or lack of their inhibitors, stimulated by immune complexes present in the structures of the basement membrane, may be responsible for destruction of anchoring fibers and blister formation. Further research is necessary in order to elucidate the question whether destruction of anchoring fibers of the basement membrane in the course of bullous diseases results from overexpression of adamalysins or lack of their inhibitors, both in skin lesions and in normally appearing skin. It would also be important to discover the probable factors activating adamalysins’ expression in lesional skin and establish the possible therapeutic use of their inhibitors.
keywords:

subepidermal bullous diseases, anchoring fibers, hemidesmosomes, basement membrane, adamalysins, metalloproteinases

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