Pemphigus an Autoimmune Disease of the Skin: Cell-Cell Separation Versus Membranal Signaling and Apoptosis in Acantholysis

Milner, Yoram; Metezeau, Philippe; Kiefer, Hélène; Finemesser, Meora; Brégégère, François; Zlotkin, Marina; Wang, Xin; Michel, Beno

doi:10.1016/b978-044482824-8/50025-7

Cited by 5 publications

(4 citation statements)

References 45 publications

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“…A further hypothesis suggests a role for intracellular signaling response, which involves the activation of phospholipase C pathway after the binding of PV-IgG to Dsg1 and 3. 7,8 Recently, Sanchez-Carpintero et al have shown that inhibitors of tyrosine kinases and phospholipase C prevented PV-IgG-induced acantholysis, lending further support to the signaling theory of acantholysis. 9 We have reported that Fas apoptotic pathway might be operative in the acantholytic process.…”

Section: Introductionmentioning

confidence: 85%

The Interaction of Pemphigus Autoimmunoglobulins with Epidermal Cells: Activation of the Fas Apoptotic Pathway and the Use of Caspase Activity for Pathogenicity Tests of Pemphigus Patients

Frušić-Zlotkin

Pergamentz

Michel³

et al. 2005

Annals of the New York Academy of Sciences

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Pemphigus is a fatal autoimmune disease in which autoimmunoglobulins PV-IgG (binding to desmoglein 3) and PF-IgG (binding to desmoglein 1) in pemphigus vulgaris and pemphigus foliaceus, respectively, cause intraepidermal blisters, cell-cell separation (acantholysis), and cell death. The mechanism of acantholytic lesion formation has not yet been elucidated. Recently, we have reported that an apoptotic mechanism might be operative in PV-IgG-induced acantholysis: (1) in patients' lesional and some perilesional skin portions, the FasR pathway is activated as its components were enriched; (2) in cultured keratinocytes, PV-IgG upregulates effectors of the FasR pathway (including the mitochondrial loop), as found by immunodetermination (cytochemistry, Western blot of pathway effectors) and determination of caspases 1, 3, and 8 activity/activation; (3) in organ cultures of skin incubated with PV-IgG, activated caspase 8 was found also in perilesional cells and coaggregated with bound PV-IgG; (4) caspase 8 activation in DISCs precedes caspase 3 activation in keratinocytes in cultures upon incubation with PV-IgG. Because caspase activation was shown to accompany lesion formation in cell and organ cultures incubated with PV-IgG, we used caspase activity to monitor the pathogenicity of PV-IgG in relation to PV-IgG binding to epithelia. A rough correlation was found between sera titers, determined by IIF and by immunoblot binding to desmoglein 3, and activation of caspase 3.

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Section: Introductionmentioning

confidence: 85%

The Interaction of Pemphigus Autoimmunoglobulins with Epidermal Cells: Activation of the Fas Apoptotic Pathway and the Use of Caspase Activity for Pathogenicity Tests of Pemphigus Patients

Frušić-Zlotkin

Pergamentz

Michel³

et al. 2005

Annals of the New York Academy of Sciences

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“…Binding of pemphigus antibody to keratinocytes stimulates multiple biochemical intracellular events, including the phosphorylation and activation of various molecules, [27][28][29][30] changes in the concentration of Ca 2131-33 and in intracellular cyclic adenosine monophosphate/cyclic guanosine monophosphate ratios 34 ; and in the expression of certain receptors 35 and markers of apoptosis and oncosis. [36][37][38][39] Elucidating which of these are primary events in acantholysis should prove a fruitful area of investigation and blocking these events could prevent acantholysis.…”

Section: Predictionsmentioning

confidence: 99%

A novel explanation for acantholysis in pemphigus vulgaris: The basal cell shrinkage hypothesis

Bystryn¹,

Grando²

2006

Journal of the American Academy of Dermatology

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“…Pemphigus immunoglobulin (Ig)G binding evokes biochemical intracellular events leading to a collapse of the cytoskeleton and cell rounding up (54,71). Activation of the cell‐death signaling pathways mediated by both caspases (apoptosis) and calpains (oncosis) has been demonstrated in KCs treated with pemphigus antibodies (72,73). Apoptosis of KCs leads to a specific cleavage of desmosomal cadherins by caspases followed by release of desmosomal cadherins from the cell surface by a metalloproteinase activity (74).…”

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confidence: 99%

Cholinergic control of epidermal cohesion

Grando

2006

Experimental Dermatology

125

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The non-neuronal cholinergic system of human epidermis includes the keratinocyte (KC) acetylcholine (ACh) axis composed of the enzymes mediating ACh synthesis and degradation, and two classes of ACh receptors, the nicotinic and muscarinic ACh receptors, mediating biological effects of the cutaneous cytotransmitter ACh. Regulation of KC cell-cell and cell-matrix adhesion is one of the important biological functions of cutaneous ACh. The downstream targets of ACh effects mediated by distinct ACh receptor subtypes include both the intercellular adhesion molecules, such as classical and desmosomal cadherins, and integrins mediating KC adhesion to a substrate. The signaling pathways include activation or inhibition of kinase cascades resulting in either up-or down-regulation of the expression of cell adhesion molecules or changes in their phosphorylation status, or both. The components of the KC ACh axis are involved in cutaneous blistering in patients with autoimmune pemphigus, junctional and dystrophic forms of epidermolysis bullosa, thermal burns, and mustard-induced vesication. Recent progress with the development of antiacantholytic therapies of patients with pemphigus using cholinomimetics indicates that cholinergic drugs may be a promising approach for other cutaneous blistering disorders.

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Pemphigus an Autoimmune Disease of the Skin: Cell-Cell Separation Versus Membranal Signaling and Apoptosis in Acantholysis

Cited by 5 publications

References 45 publications

The Interaction of Pemphigus Autoimmunoglobulins with Epidermal Cells: Activation of the Fas Apoptotic Pathway and the Use of Caspase Activity for Pathogenicity Tests of Pemphigus Patients

The Interaction of Pemphigus Autoimmunoglobulins with Epidermal Cells: Activation of the Fas Apoptotic Pathway and the Use of Caspase Activity for Pathogenicity Tests of Pemphigus Patients

A novel explanation for acantholysis in pemphigus vulgaris: The basal cell shrinkage hypothesis

Cholinergic control of epidermal cohesion

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