Both early and late apoptotic blebs are taken up by DC and induce IL-6 production.
During apo blebs, containing nuclear components, are formed at the cells' surfaces. When these blebs separate from the dying cell an apo cell body remains. The contents of apo blebs are modified and can be released, especially in patients with systemic lupus erythematosus (SLE) since impaired clearance of apo material has been observed in this autoimmune condition. Accordingly, autoantibodies present in subjects with SLE bind to apo blebs. Based on AnxA5 binding, and permeability for PI, we show that apo blebs can be categorized as early (AnxA5(+)/PI(- )) or late (AnxA5(+)/PI(+)) apo ones. Both forms of blebs contain apo-induced chromatin modifications and are efficiently phagocytosed by dendritic cell (DC). Uptake by DC of late, but also early apo blebs, stimulate DC to produce IL-6. This bleb-induced effect on DC may be an important step in the initiation of the autoimmune responses in SLE.
Fransen
J H
JH
Nephrology Research Laboratory, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Hilbrands
L B
LB
Jacobs
C W
CW
Adema
G J
GJ
Berden
J H
JH
Van der Vlag
J
J
D000818:Animals; D017304:Annexin A5 / Q000276:immunology / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010587:Phagocytosis / Q000276:immunology
D017304:Annexin A5; D001323:Autoantibodies; D001324:Autoantigens; D015850:Interleukin-6