Article

Pemphigus IgG causes skin splitting in the presence of both desmoglein 1 and desmoglein 3

University of Würzburg, Institute of Anatomy and Cell Biology, Würzburg, Germany.
American Journal Of Pathology (Impact Factor: 4.6). 10/2007; 171(3):906-16. DOI: 10.2353/ajpath.2007.070028
Source: PubMed

ABSTRACT According to the desmoglein (Dsg) compensation concept, different epidermal cleavage planes observed in pemphigus vulgaris and pemphigus foliaceus have been proposed to be caused by different autoantibody profiles against the desmosomal proteins Dsg 1 and Dsg 3. According to this model, Dsg 1 autoantibodies would only lead to epidermal splitting in those epidermal layers in which no Dsg 3 is present to compensate for the functional loss of Dsg 1. We provide evidence that both pemphigus foliaceus-IgG containing Dsg 1- but not Dsg 3-specific antibodies and pemphigus vulgaris-IgG with antibodies to Dsg 1 and Dsg 3 were equally effective in causing epidermal splitting in human skin and keratinocyte dissociation in vitro. These effects were present where keratinocytes expressed both Dsg 1 and Dsg 3, demonstrating that Dsg 3 does not compensate for Dsg 1 inactivation. Rather, the cleavage plane in intact human skin caused by pemphigus autoantibodies was similar to the plane of keratinocyte dissociation in response to toxin B-mediated inactivation of Rho GTPases. Because we recently demonstrated that pemphigus-IgG causes epidermal splitting by inhibition of Rho A, we propose that Rho GTPase inactivation contributes to the mechanisms accounting for the cleavage plane in pemphigus skin splitting.

0 Followers
 · 
115 Views
  • Source
    • "At 48 hours after transfections, the cells were incubated with 30 mmol l –1 SB202190, a specific inhibitor of p38MAPK for 6 hours. Next, cells were fixed with 2% formalin (freshly prepared from paraformaldehyde) for 10 minutes and subjected to immunostaining procedures as described in detail elsewhere (Spindler et al., 2007). Mouse monoclonal Pg Ab (Progen), rabbit polyclonal DP Ab (NW6, a kind gift of Dr Kathleen Green, Northwestern University, Chicago, IL), FITC-conjugated pancytokeratin mAb (Sigma-Aldrich), or pan-cytokeratin E605 mAb (Ebioscience, San Diego, CA) was used as the primary Ab. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Plakoglobin (Pg) and desmoplakin (DP) are adapter proteins within the desmosome, providing a mechanical link between desmosomal cadherins as transmembrane adhesion molecules and the intermediate filament cytoskeleton. Because in the severe skin blistering disease pemphigus autoantibodies against desmosomal adhesion molecules induce loss of keratinocyte cohesion at least in part via p38MAPK activation and depletion of desmosomal components, we evaluated the roles of Pg and DP in p38MAPK-dependent loss of cell adhesion. Silencing of either Pg or DP reduced cohesion of cultured human keratinocytes in dissociation assays. However, Pg but not DP silencing caused activation of p38MAPK-dependent keratin filament collapse and cell dissociation. Interestingly, extranuclear but not nuclear Pg rescued loss of cell adhesion and keratin retraction. In line with this, Pg regulated the levels of the desmosomal adhesion molecule desmoglein 3 and tethered p38MAPK to desmosomal complexes. Our data demonstrate a role of extranuclear Pg in controlling cell adhesion via p38MAPK-dependent regulation of keratin filament organization.Journal of Investigative Dermatology accepted article preview online, 17 January 2014. doi:10.1038/jid.2014.21.
    Journal of Investigative Dermatology 01/2014; 134(6). DOI:10.1038/jid.2014.21 · 6.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: CoCoon is a tool embodying the idea of space devoted to a function for the specification process of graphic user interfaces (GUIs). The functional space is called widegap, standing for conceptual widget, being the user interface designer reasoning about logical components of the user interface. Using interface designers partition the work space by using widgepts and specify them in terms of their attributes. In so doing, they exploit some cliches, or stereotypes, called k-stereotypes, representing the CoCoon level of abstraction. A translator module builds a hierarchical tree which records spatial relations between widgepts and then maps k-stereotypes onto a library of reusable modules, called M-stereotypes. The overall result is the automatic generation of code, by merging M-stereotypes. The authors discuss the motivation, the approach, the architecture and the operation of CoCoon
  • [Show abstract] [Hide abstract]
    ABSTRACT: A review is given of (mainly recent) work on the biodiversity, ecology, biogeography and practical importance of marine parasites. Problems in estimating species numbers have been thoroughly discussed for free-living species, and the main points of these discussions are reviewed here. Even rough estimates of the richness of most parasite groups in the oceans are premature for the following reasons: species numbers of host groups, in particular in the deep sea and the meiofauna, are not known; most host groups have been examined only insufficiently for parasites or not at all; even in some of the best known groups, latitudinal, longitudinal and depth gradients in species richness are only poorly understood or not known at all; effects of hosts on parasite morphology and geographical variation have been studied only in a few cases; there are few studies using techniques of molecular biology to distinguish sibling species. Estimates of species richness in the best known groups, trematodes, monogeneans and copepods of marine fishes, are given. Parasites are found in almost all taxa of eukaryotes, but most parasitic species are concentrated in a few taxa. Important aspects of the ecology of marine parasites are discussed. It is emphasized that host specificity and host ranges should be distinguished, and an index that permits calculation of host specificity is discussed. The same index can be applied to measure site specificity. Central problems in ecology are the importance of interspecific competition and whether equilibrium or non-equilibrium conditions prevail. Marine parasites are among the few groups of organisms that have been extensively examined in this regard. A holistic approach, i.e. application of many methods, has unambiguously shown that metazoan ecto- (and probably endo-) parasites of marine fish live in largely non-saturated niche space under non-equilibrium conditions, i.e. they live in assemblages rather than in communities structured by competition. Nestedness occurs in such assemblages, but it can be explained by characteristics of the species themselves. There is little agreement on which other factors are involved in "structuring" parasite assemblages. Few studies on metapopulations of marine parasites have been made. A new approach, that of fuzzy chaos modelling, is discussed. It is likely that marine parasites are commonly found in metapopulations consisting of many subpopulations, and they are ideally suited to test the predictions of fuzzy chaos. Some recent studies on functional ecology and morphology--especially with regard to host, site and mate finding--are discussed, and attention is drawn to the amazing variety of sensory receptors in some marine parasites. Effects of parasites on hosts, and some studies on the evolution and speciation of marine parasites are discussed as well. A detailed overview of biogeographical studies is given, with respect to latitudinal gradients in species diversity, reproductive strategies and host ranges/specificity. Studies of marine parasites have contributed significantly to giving a non-equilibrium explanation for latitudinal diversity gradients. Recent studies on longitudinal and depth gradients are discussed, as well as parasites in brackish water, parasites as indicators of zoogeographical regions and barriers, and parasites as biological tags. The practical importance of marine parasites in mariculture, as monitors of pollution, agents of human disease, the use of parasites for controlling introduced marine pests, and some related aspects, are also discussed.
    Advances in Marine Biology 02/2002; 43:1-86. DOI:10.1016/S0065-2881(02)43002-7 · 5.00 Impact Factor
Show more

Preview

Download
0 Downloads
Available from