Apoptosis in different cutaneous manifestations of lupus erythematosus.
BACKGROUND
It has been shown that dysregulation of apoptosis may play an important part in the development of autoimmune diseases such as lupus erythematosus (LE).


OBJECTIVE
The aim of the study was to investigate whether apoptosis may contribute to the pathogenesis of cutaneous changes in LE and whether certain apoptosis-related markers such as Fas antigen, Fas ligand (FasL), Bcl-2 and Bax proteins take part in this process.


METHODS
Cryostat sections of lesional skin from 31 patients with LE-specific skin lesions [discoid (DLE) n = 17, subacute cutaneous (SCLE) n = 10 and acute cutaneous (ACLE) n = 4] and normal skin samples (n = 10) were stained with monoclonal antibodies against Fas antigen, FasL, Bcl-2 and Bax proteins. For the detection of apoptotic nuclei, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling technique (TUNEL) was employed.


RESULTS
The keratinocytes of the epidermis and mononuclear cells of the dermal infiltrate in LE showed a significant increase in Fas antigen expression as compared with normal skin. The anti-Bcl-2 staining intensity within the epidermis was markedly decreased, while the mononuclear infiltrate stained for this protein just like single lymphocytes scattered in normal skin. There was an increase of FasL and/or Bax-positive cells within the dermal infiltrate, but not in the epidermis or in the hair follicles. Accumulation of FasL-bearing cells around hair follicles was a hallmark of DLE. Numerous cells with pyknotic, TUNEL-positive nuclei were demonstrated in the epidermis, in hair follicles and among the cells of the dermal infiltrate. The extent of apoptosis in lesional skin was greater in acute and subacute cutaneous than in discoid forms of LE.


CONCLUSIONS
The exact stimulus triggering apoptosis in cutaneous LE still remains unknown but the present study provides strong evidence that the reduction of Bcl-2 expression in the basal cells is associated with the overexpression of Fas antigen and correlates directly with the extent of apoptosis in the epidermis. Furthermore, the current study indicates that the extent of apoptosis in both the epidermis and dermal infiltrate may correlate with the chronological development of LE skin lesions.
Baima
B
B
Department of Dermatology, University of Kiel, Schittenhelmstrasse 7, 24105 Kiel, Germany. bbaima@dermatology.uni-kiel.de
Sticherling
M
M
D017209:Apoptosis / Q000502:physiology*; D004817:Epidermis / Q000378:metabolism; D053222:Fas Ligand Protein; D006801:Humans; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D008024:Ligands; D008178:Lupus Erythematosus, Cutaneous / Q000378:metabolism / Q000473:pathology*; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D051028:bcl-2-Associated X Protein; D019014:fas Receptor / Q000378:metabolism
C494826:BAX protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008024:Ligands; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D019014:fas Receptor