Epidermolysis bullosa acquisita antigen is the globular carboxyl terminus of type VII procollagen.

Woodley, David T.; Burgeson, Robert E.; Lunstrum, Gregory P.; Bruckner‐Tuderman, Leena; Reese, Melinda J.; Briggaman, Robert A.

doi:10.1172/jci113373

Cited by 321 publications

(150 citation statements)

References 32 publications

(38 reference statements)

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“…The hemidesmosome and the anchoring fibril are also important ultrastructures within the BMZ, which serve to unite the epidermis and dermis [4,23]. Laminin 5 and type XVII collagen are thought to constitute the hemidesmosome [3,20], and type VII collagen is a major component of anchoring fibrils [32]. With immunohistochemical analysis of the present study, the presence of the basement membrane was verified in most regions by type IV collagenpositive reactions.…”

Section: Discussionsupporting

confidence: 57%

Unilateral Basement Membrane Zone Alteration of the Regenerated Laminar Region in Equine Chronic Laminitis

et al. 2005

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ABSTRACT. Between the laminar epidermis and the laminar dermis of laminar region (LR) in equine foot, it can be observed the basement membrane zone (BMZ), which is composed of a basement membrane and its accompaniments like the hemidesmosome and anchoring fibril. Alteration in the BMZ in equine laminitis is possibly related with not only development but also recovery outcome and recurrence of this disease. However, there is little known about the structure of the BMZ during the recovery phase of this disease. To assess the condition of the BMZ of LR affected by chronic laminitis, the tissue was examined in three cases at two weeks, four weeks and three months after the onset of laminitis, using pathological, immunohistochemical and electron microscopic techniques. Histologically in all laminitis cases, there was a regenerated laminar epidermis with proliferating keratinocytes between the Stratum medium and the dermis, but it included the undeveloped secondary epidermal laminae (ud-SELs) structure in one side of the primary epidermal laminae, especially in the part of the deep area of LR. Immunohistochemical results were positive for the anti-type IV collagen, anti-type VII collagen and anti-laminin 5 antibodies in the most BMZs. However, partial BMZs adjacent to the ud-SELs were negative for the anti-type VII collagen and anti-laminin 5 antibodies. Ultrastructurally, in the BMZ of the ud-SEL, the lamina densa and the lamina lucida were present. In contrast, the anchoring fibrils and the hemidesmosomes were either absent, or present at lower than normal levels. In conclusion, the present study indicated that the part of regenerated LR in chronic laminitis was not able to fully restore to construct the BMZ for a long time, especially in the unilateral side of laminar epidermis. It might be related with recurrence of this disease. KEY WORDS: basement membrane zone, chronic laminitis, collagen, equine, laminin 5.J. Vet. Med. Sci. 67 (7): [685][686][687][688][689][690][691] 2005 The integumental tissues of the foot are important in supporting the horse's entire body weight during static and dynamic loading conditions. If severe intractable hoof disease occurs, the horse may lose not only the ability to run, but also to stand. Laminitis is one such intractable hoof condition and has a recurrent nature. Many horses have suffered from this disease over extended periods, resulting in significant treatment costs, and therefore the equine industry has a great deal of interest in clarifying the pathogenesis and developing treatment methods [5,9,12].Anatomically, the laminar region in foot displays a complex 3-dimensional structure consisting of the primary epidermal lamina (PEL) and the secondary epidermal lamina (SEL) which interdigitate with their dermal counterparts [24]. These dermal and epidermal components are separated by the basement membrane zone (BMZ), which is composed of a basement membrane and its accompaniments like the hemidesmosome and anchoring fibril [23]. The hemidesmosome, anchoring fibril and other c...

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Section: Discussionsupporting

confidence: 57%

Unilateral Basement Membrane Zone Alteration of the Regenerated Laminar Region in Equine Chronic Laminitis

et al. 2005

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“…In EBA, blister formation depends on and is initiated by the binding of autoantibodies to COL7, located at the dermal-epidermal junction (29,30). Subsequently, Fc-dependent mechanisms result in the formation of a proinflammatory milieu in the skin (31).…”

Section: Discussionmentioning

confidence: 99%

Caspase-1–Independent IL-1 Release Mediates Blister Formation in Autoantibody-Induced Tissue Injury through Modulation of Endothelial Adhesion Molecules

Sadeghi

Lockmann

Hund

et al. 2015

The Journal of Immunology

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Although reports documented aberrant cytokine expression in autoimmune bullous dermatoses (AIBDs), cytokine-targeting therapies have not been established in these disorders. We showed previously that IL-6 treatment protected against tissue destruction in experimental epidermolysis bullosa acquisita (EBA), an AIBD caused by autoantibodies to type VII collagen (COL7). The anti-inflammatory effects of IL-6 were mediated by induction of IL-1ra, and prophylactic IL-1ra administration prevented blistering. In this article, we demonstrate elevated serum concentrations of IL-1β in both mice with experimental EBA induced by injection of anti-COL7 IgG and in EBA patients. Increased IL-1α and IL-1β expression also was observed in the skin of anti-COL7 IgG-injected wild-type mice compared with the significantly less diseased IL-1R–deficient or wild-type mice treated with the IL-1R antagonist anakinra or anti–IL-1β. These findings suggested that IL-1 contributed to recruitment of inflammatory cells into the skin. Accordingly, the expression of ICAM-1 was decreased in IL-1R–deficient and anakinra-treated mice injected with anti-COL7. This effect appeared to be specifically attributable to IL-1 because anakinra blocked the upregulation of different endothelial adhesion molecules on IL-1–stimulated, but not on TNF-α–stimulated, cultured endothelial cells. Interestingly, injection of caspase-1/11–deficient mice with anti-COL7 IgG led to the same extent of skin lesions as in wild-type mice. Collectively, our data suggest that IL-1, independently of caspase-1, contributes to the pathogenesis of EBA. Because anti–IL-1β in a prophylactic setting and anakinra in a quasi-therapeutic setting (i.e., when skin lesions had already developed) improved experimental EBA, IL-1 appears to be a potential therapeutic target for EBA and related AIBDs.

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“…This highly interwoven network of fibrils is obviously well able to stabilize basement membrane connections in tissues which are exposed to considerable shearing forces [162]. Such connections are sevcrly disturbed in patients with epidermolysis bullosa acquisita, a severe and chronic blistering disease, apparently due to autoantibodies against the NCI domain of collagen VII [163].…”

Section: Collagen Type VIImentioning

confidence: 99%

Structure and biological activity of basement membrane proteins

Timpl

1989

European Journal of Biochemistry

926

394

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Collagen type IV, laminin, heparan sulfate proteoglycans, nidogen (entactin) and SPARC) represent major structural proteins of basement membranes. They are well-characterized in their domain structures, amino acid sequences and potentials for molecular interactions. Such interactions include self-assembly processes and heterotypic binding between individual constituents, as well as binding of calcium (laminin, and are likely to be used for basement membrane assembly. Laminin, collagen IV and nidogen also possess several cell-binding sites which interact with distinct cellular receptors. Some evidence exists that those interactions are involved in the control of cell behaviour. These observations have provided a more defined understanding of basement membrane function and the definition of new research goals in the future.All multicellular animals possess various extracellular matrices. They determine body shape and stability, compartmentalization of organs and several cellular activities. These matrices include ubiquitously occurring basement membranes which are 20 -200-nm-broad deposits of some specific proteins in close proximity to epithelial, muscle, fat and nerve cells. Basement membranes are found in vertebrates and invertebrates except sponges and are produced as the first matrix during embryonic development. They are considered to control cell phenotype, tissue invasion of cells and filtration of macromolecules through glomeruli [I -41. This implies a defined supramolecular architecture for basement membranes and a distinct repertoire of biological activities expressed as the sum of their individual constituents. Yet, electron microscopy has so far revealed few details of basement membrane structure which, after staining, presents as two amorphous zones (the lamina lucida and the lamina densa) distinguished by different electron densities [5].Basement membranes are normally but not exclusively produced and deposited by cells which then remain in close contact with these structures. These contacts are mediated by specific cellular receptors which bind to some defined extracellular ligands [l -31. Other noncovalent molecular interactions maintain the matrix structure and covalent cross-links make basement membranes rather insoluble even in denaturing solvents. The increasing use of tumor models, such as the Engelbreth-Holm-Swarm (EHS) mouse tumor [6], which produce large amounts of soluble basement-membrane material has over the past decade allowed a comprehensive characterization of the major components. The progress in our understanding of the structure, biology and pathology of basement membranes 11-5 , 7 -101 as well as some methodological aspects [lo, 111 have been recently reviewed. The preCorrespondence to R . Timpl.

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Epidermolysis bullosa acquisita antigen is the globular carboxyl terminus of type VII procollagen.

Cited by 321 publications

References 32 publications

Unilateral Basement Membrane Zone Alteration of the Regenerated Laminar Region in Equine Chronic Laminitis

Unilateral Basement Membrane Zone Alteration of the Regenerated Laminar Region in Equine Chronic Laminitis

Caspase-1–Independent IL-1 Release Mediates Blister Formation in Autoantibody-Induced Tissue Injury through Modulation of Endothelial Adhesion Molecules

Structure and biological activity of basement membrane proteins

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