Disruption of the cytoskeleton after apoptosis induction with autoantibodies.
F-actin cleavage was studied in PBMC after treatment with anti-dsDNA antibodies. Significant changes in F-actin disruption detected by decrease of FITC-phalloidin staining occurred after apoptosis induction with anti-dsDNA antibodies (p < 0.006). Despite of similar F-actin disruption, the switch of phosphatidylserine (PS) to the outer leaflet of the cell membrane as detected by annexin V binding was lower after anti-dsDNA antibody than without antibody treatment (58.4 +/- 11.0% vs. 81.9 +/- 7.7%). F-actin disruption was accompanied by activation of caspase 3 within the cytoplasm (r = -0.92599; p < 8.87446 x 10-(10)) under both conditions with and without autoantibodies. These findings indicate that anti-dsDNA antibody-induced apoptosis is more marked within the cell than upon the cell surface. The diminished externalization of PS might result in a decreased phagocytosis. Thereby, the reduced clearance of apoptotic cells could induce autoantibody production possibly against epitopes which arise due to the apoptotic disruption of cells.
Böhm
Ingrid
I
Department of Radiology, University of Bonn, Sigmund-Freud Strasse 25, 53105 Bonn, Germany. i.boehm@uni-bonn.de
D000199:Actins / Q000276:immunology / Q000378:metabolism; D000328:Adult; D000368:Aged; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology / Q000502:physiology*; D001323:Autoantibodies / Q000276:immunology / Q000378:metabolism*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D003599:Cytoskeleton / Q000276:immunology / Q000378:metabolism*; D004247:DNA / Q000276:immunology; D053938:DNA Fragmentation / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010590:Phalloidine; D013194:Staining and Labeling
D000199:Actins; D017304:Annexin A5; D001323:Autoantibodies; D010590:Phalloidine; D004247:DNA; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases