PMID- 18987254
OWN - NLM
STAT- MEDLINE
DCOM- 20090226
LR  - 20220317
IS  - 0363-6143 (Print)
IS  - 0363-6143 (Linking)
VI  - 296
IP  - 1
DP  - 2009 Jan
TI  - Apoptosis is not required for acantholysis in pemphigus vulgaris.
PG  - C162-72
LID - 10.1152/ajpcell.00161.2008 [doi]
AB  - The autoimmune blistering skin disease pemphigus vulgaris (PV) is caused 
      primarily by autoantibodies against desmosomal cadherins. It was reported that 
      apoptosis can be detected in pemphigus skin lesions and that apoptosis can be 
      induced by PV-IgG in cultured keratinocytes. However, the role of apoptosis in PV 
      pathogenesis is unclear at present. In this study, we provide evidence that 
      apoptosis is not required for acantholysis in PV. In skin lesions from two PV 
      patients, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling 
      (TUNEL) positivity, but not cleaved caspase-3, was detected in single 
      keratinocytes in some lesions but was completely absent in other lesions from the 
      same patients. In cultures of human keratinocytes (HaCaT and normal human 
      epidermal keratinocytes), PV-IgG from three different PV patients caused 
      acantholysis, fragmented staining of Dsg 3 staining, and cytokeratin retraction 
      in the absence of nuclear fragmentation, TUNEL positivity, and caspase-3 cleavage 
      and hence in the absence of detectable apoptosis. To further rule out the 
      contribution of apoptotic mechanisms, we used two different approaches that are 
      effective to block apoptosis induced by various stimuli. Inhibition of caspases 
      by z-VAD-fmk as well as overexpression of Fas-associated death domain-like 
      interleukin-1beta-converting enzyme (FLICE)-like inhibitory proteins FLIP(L) and 
      FLIP(S) to inhibit receptor-mediated apoptosis did not block PV-IgG-induced 
      effects, indicating that apoptosis was not required. Taken together, we conclude 
      that apoptosis is not a prerequisite for skin blistering in PV but may occur 
      secondary to acantholysis.
FAU - Schmidt, Enno
AU  - Schmidt E
AD  - Department of Dermatology, University of Wurzburg, Wurzburg, Germany.
FAU - Gutberlet, Judith
AU  - Gutberlet J
FAU - Siegmund, Daniela
AU  - Siegmund D
FAU - Berg, Daniela
AU  - Berg D
FAU - Wajant, Harald
AU  - Wajant H
FAU - Waschke, Jens
AU  - Waschke J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20081105
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (Amino Acid Chloromethyl Ketones)
RN  - 0 (CASP8 and FADD-Like Apoptosis Regulating Protein)
RN  - 0 (Cysteine Proteinase Inhibitors)
RN  - 0 (DSG3 protein, human)
RN  - 0 (Desmoglein 3)
RN  - 0 (Immunoglobulin G)
RN  - 0 (benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone)
RN  - 68238-35-7 (Keratins)
RN  - EC 3.4.22.- (CASP3 protein, human)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Acantholysis/immunology/metabolism/*pathology
MH  - Amino Acid Chloromethyl Ketones/pharmacology
MH  - Anoikis
MH  - *Apoptosis/drug effects
MH  - Biopsy
MH  - CASP8 and FADD-Like Apoptosis Regulating Protein/genetics/metabolism
MH  - Caspase 3/metabolism
MH  - Cell Line
MH  - Cell Nucleus Shape
MH  - Cysteine Proteinase Inhibitors/pharmacology
MH  - DNA Fragmentation
MH  - Desmoglein 3/metabolism
MH  - Humans
MH  - Immunoglobulin G/*blood
MH  - Immunohistochemistry
MH  - In Situ Nick-End Labeling
MH  - Keratinocytes/drug effects/immunology/metabolism/*pathology
MH  - Keratins/metabolism
MH  - Pemphigus/immunology/metabolism/*pathology
MH  - Transfection
EDAT- 2008/11/07 09:00
MHDA- 2009/02/27 09:00
CRDT- 2008/11/07 09:00
PHST- 2008/11/07 09:00 [pubmed]
PHST- 2009/02/27 09:00 [medline]
PHST- 2008/11/07 09:00 [entrez]
AID - 00161.2008 [pii]
AID - 10.1152/ajpcell.00161.2008 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2009 Jan;296(1):C162-72. doi: 
      10.1152/ajpcell.00161.2008. Epub 2008 Nov 5.