Remnants of secondarily necrotic cells fuel inflammation in systemic lupus erythematosus

作者: Luis E Munoz , Christina Janko , Gerhard E Grossmayer , Benjamin Frey , Reinhard E Voll

DOI: 10.1002/ART.24535

关键词:

摘要: Objective Patients with systemic lupus erythematosus (SLE) are often characterized by cellular as well humoral deficiencies in the recognition and phagocytosis of dead dying cells. The aim this study was to investigate whether remnants apoptotic cells involved induction inflammatory cytokines blood-borne phagocytes. Methods We used ex vivo assays comprising components isolated granulocytes monocytes secondarily necrotic cell–derived material (SNEC). Cytokines were measured multiplex bead array technology. Results We confirmed impaired uptake various particulate targets, including immunoglobulin-opsonized beads, from patients SLE compared healthy control subjects. Surprisingly, phagocytes two-thirds took up SNEC, which rarely phagocytosed subjects or rheumatoid arthritis. Supplementation donor blood IgG fractions derived transferred capability take SNEC donors. Phagocytosis-promoting immune globulins also induced secretion huge amounts following SNEC. Conclusion Opsonization autoantibodies fosters its granulocytes. Autoantibody-mediated is accompanied cytokines, fueling inflammation that contributes perpetuation autoimmunity SLE.

参考文章(38)
John van de Erve, Creeping eruption, systemic therapy. Journal of Investigative Dermatology. ,vol. 12, pp. 69- 79 ,(1949) , 10.1038/JID.1949.10
R P Kimberly, M Fotino, A Gibofsky, J E Salmon, Defective mononuclear phagocyte function in systemic lupus erythematosus: dissociation of Fc receptor-ligand binding and internalization. Journal of Immunology. ,vol. 133, pp. 2525- 2531 ,(1984)
Reinhard E. Voll, Martin Herrmann, Edith A. Roth, Christian Stach, Joachim R. Kalden, Irute Girkontaite, Immunosuppressive effects of apoptotic cells Nature. ,vol. 390, pp. 350- 351 ,(1997) , 10.1038/37022
Lorenza Frisoni, Lenese Mcphie, Lucrezia Colonna, Uma Sriram, Marc Monestier, Stefania Gallucci, Roberto Caricchio, Nuclear autoantigen translocation and autoantibody opsonization lead to increased dendritic cell phagocytosis and presentation of nuclear antigens: a novel pathogenic pathway for autoimmunity? Journal of Immunology. ,vol. 175, pp. 2692- 2701 ,(2005) , 10.4049/JIMMUNOL.175.4.2692
L. F. Sarmiento, L. F. Sarmiento, L. E. Muñoz, L. F. Sarmiento, L. E. Muñoz, P. Chirinos, N. E. Bianco, M. E. Zabaleta-Lanz, Opsonization by anti-dsDNA antibodies of apoptotic cells in systemic lupus erythematosus. Autoimmunity. ,vol. 40, pp. 337- 339 ,(2007) , 10.1080/08916930701356663
Alastair L Hepburn, Irvin A Lampert, Joseph J Boyle, Donna Horncastle, W Fai Ng, Mark Layton, Timothy J Vyse, Marina Botto, Justin C Mason, In vivo evidence for apoptosis in the bone marrow in systemic lupus erythematosus Annals of the Rheumatic Diseases. ,vol. 66, pp. 1106- 1109 ,(2007) , 10.1136/ARD.2006.065003
A Perniok, F Wedekind, M Herrmann, C Specker, M Schneider, High levels of circulating early apoptic peripheral blood mononuclear cells in systemic lupus erythematosus Lupus. ,vol. 7, pp. 113- 118 ,(1998) , 10.1191/096120398678919804
John R. Haserick, Donald W. Bortz, Normal Bone Marrow Inclusion Phenomena Induced by Lupus Erythematosus Plasma Journal of Investigative Dermatology. ,vol. 13, pp. 47- 49 ,(1949) , 10.1038/JID.1949.65
Kohki Kawane, Mayumi Ohtani, Keiko Miwa, Takuji Kizawa, Yoshiyuki Kanbara, Yoshichika Yoshioka, Hideki Yoshikawa, Shigekazu Nagata, Chronic polyarthritis caused by mammalian DNA that escapes from degradation in macrophages Nature. ,vol. 443, pp. 998- 1002 ,(2006) , 10.1038/NATURE05245
Patrizia Rovere, Maria Grazia Sabbadini, Cristina Vallinoto, Umberto Fascio, Maria Rescigno, Mariacristina Crosti, Paola Ricciardi-Castagnoli, Genesio Balestrieri, Angela Tincani, Angelo A. Manfredi, Dendritic cell presentation of antigens from apoptotic cells in a proinflammatory context: Role of opsonizing anti–β2‐glycoprotein I antibodies Arthritis & Rheumatism. ,vol. 42, pp. 1412- 1420 ,(1999) , 10.1002/1529-0131(199907)42:7<1412::AID-ANR15>3.0.CO;2-T