Serum DNase I, soluble Fas/FasL levels and cell surface Fas expression in patients with SLE: a possible explanation for the lack of efficacy of hrDNase I treatment.
The objectives of the study are to evaluate DNase I serum levels and their correlation with soluble Fas (sFas) and soluble Fas ligand (sFasL) and with cell surface Fas expression in patients with systemic lupus erythematosus (SLE), thus contributing to the dysregulated apoptosis typical of the disease. The methods include the following: Serum DNase I levels in patients and in controls were detected using the dot blot method and quantified by densitometry; sFas and sFasL were quantified using an ELISA system. Cell surface Fas expression was evaluated by FACS analysis. Apoptosis was studied by means of internucleosomal DNA degradation using a commercially available kit. The results are as follows: We found a significant difference in DNase I, sFas and sFasL serum levels between patients and controls. Levels of DNase I <7.79 ng ml(-1) are more represented in patients with SLE. Active SLE is strongly associated with high sFas levels and detectable sFasL. DNase I does not correlate with sFas or sFasL, whereas it correlates with T cell surface Fas expression that is higher in patients with active SLE than in healthy controls. Finally, administration of exogenous human recombinant DNase (hrDNase) I to freshly isolated T cells up-regulates cell surface Fas expression and induces increased susceptibility to Fas-mediated apoptosis. In conclusion, our findings confirm that DNase I is low in SLE and suggest that it may play a role in apoptosis in SLE by regulating the surface expression of the cell death molecule Fas. This role may contribute to explain the inefficacy of hrDNase I in SLE, a treatment proposed for the ability of DNase I to remove DNA from auto-antigenic nucleoprotein complexes.
Tinazzi
Elisa
E
Department of Clinical and Experimental Medicine, Section of Internal Medicine, University of Verona, 37134 Verona, Italy.
Puccetti
Antonio
A
Gerli
Roberto
R
Rigo
Antonella
A
Migliorini
Paola
P
Simeoni
Sara
S
Beri
Ruggero
R
Dolcino
Marzia
M
Martinelli
Nicola
N
Corrocher
Roberto
R
Lunardi
Claudio
C
D000328:Adult; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D002469:Cell Separation; D002478:Cells, Cultured; D003850:Deoxyribonuclease I / Q000097:blood / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use; D053222:Fas Ligand Protein / Q000097:blood / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000097:blood / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D019014:fas Receptor / Q000097:blood* / Q000235:genetics / Q000276:immunology
C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D011994:Recombinant Proteins; D019014:fas Receptor; D003850:Deoxyribonuclease I