TY - JOUR
T1 - Dendritic cells preferentially internalize apoptotic cells opsonized by anti-β2-glycoprotein I antibodies
AU - Rovere, Patrizia
AU - Manfredi, Angelo A.
AU - Vallinoto, Cristina
AU - Zimmermann, Valerie S.
AU - Fascio, Umberto
AU - Balestrieri, Genesio
AU - Ricciardi-Castagnoli, Paola
AU - Rugarli, Claudio
AU - Tincani, Angela
AU - Sabbadini, Maria Grazia
PY - 1998/10
Y1 - 1998/10
N2 - Dendritic cells (DC) are potent antigen-presenting cells involved in the initiation of immune responses, including those directed towards self antigens, Immature DC capture soluble antigens by macropinocytosis or c-type lectin receptor-mediated endocytosis and particulate by phagocytosis, including Fc receptor-mediated phagocytosis. Apoptosis is accompanied by the clustering of intracellular autoantigens, which are also selectively cleaved and phosphorylated, and by the exposure of anionic phospholipids (phosphatidylserine, PS). Anti-phospholipid antibody (aPL) detection correlates with an increased risk of developing autoimmune syndromes. In this study apoptosis was induced by UV irradiation, growth factor deprivation or exposure to protein synthesis inhibitors of murine cells and verified by confocal microscopy and flow cytometry. Apoptotic cells were recognized by a panel of anti-β2-glycoprotein I (β2-GPI) aPL monoclonal antibodies, but not by isotype-matched antibodies. The binding restricted to membrane domains, corresponding to apoptotic blebs, was not affected by the stimulus initiating apoptosis and was specific, since it required the association of the β2-GPI co-factor to the apoptotic membrane. aPL-binding successfully transformed apoptotic cells in an efficient phagocytic substrate for murine immature DC, possibly skewing their immunogenicity in vivo.
AB - Dendritic cells (DC) are potent antigen-presenting cells involved in the initiation of immune responses, including those directed towards self antigens, Immature DC capture soluble antigens by macropinocytosis or c-type lectin receptor-mediated endocytosis and particulate by phagocytosis, including Fc receptor-mediated phagocytosis. Apoptosis is accompanied by the clustering of intracellular autoantigens, which are also selectively cleaved and phosphorylated, and by the exposure of anionic phospholipids (phosphatidylserine, PS). Anti-phospholipid antibody (aPL) detection correlates with an increased risk of developing autoimmune syndromes. In this study apoptosis was induced by UV irradiation, growth factor deprivation or exposure to protein synthesis inhibitors of murine cells and verified by confocal microscopy and flow cytometry. Apoptotic cells were recognized by a panel of anti-β2-glycoprotein I (β2-GPI) aPL monoclonal antibodies, but not by isotype-matched antibodies. The binding restricted to membrane domains, corresponding to apoptotic blebs, was not affected by the stimulus initiating apoptosis and was specific, since it required the association of the β2-GPI co-factor to the apoptotic membrane. aPL-binding successfully transformed apoptotic cells in an efficient phagocytic substrate for murine immature DC, possibly skewing their immunogenicity in vivo.
KW - Anti-phospholipid antibody
KW - Anti-phospholipid antibody syndrome
KW - Apoptosis
KW - Dendritic cells
KW - Systemic lupus erythematosus
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U2 - 10.1006/jaut.1998.0224
DO - 10.1006/jaut.1998.0224
M3 - Article
C2 - 9802923
AN - SCOPUS:0032192041
VL - 11
SP - 403
EP - 411
JO - Journal of Autoimmunity
JF - Journal of Autoimmunity
SN - 0896-8411
IS - 5
ER -