Research output: Contribution to journal › Article › peer-review
Changes in cell differentiation and proliferation lead to production of abzymes in EAE mice treated with DNA–Histone complexes. / Aulova, Kseniya S.; Toporkova, Ludmila B.; Lopatnikova, Julia A. et al.
In: Journal of Cellular and Molecular Medicine, Vol. 22, No. 12, 01.12.2018, p. 5816-5832.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Changes in cell differentiation and proliferation lead to production of abzymes in EAE mice treated with DNA–Histone complexes
AU - Aulova, Kseniya S.
AU - Toporkova, Ludmila B.
AU - Lopatnikova, Julia A.
AU - Alshevskaya, Alina A.
AU - Sedykh, Sergey E.
AU - Buneva, Valentina N.
AU - Budde, Thomas
AU - Meuth, Sven G.
AU - Popova, Nelly A.
AU - Orlovskaya, Irina A.
AU - Nevinsky, Georgy A.
N1 - Publisher Copyright: © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Experimental autoimmune encephalomyelitis (EAE)-prone C57BL/6 mice are used as a model of human multiple sclerosis. We immunize mice with myelin oligodendrocyte glycoprotein (MOG), DNA–histone and DNA-methylated bovine serum albumin (met-BSA) complexes to reveal different characteristics of EAE development including bone marrow lymphocyte proliferation and differentiation profiles of hematopoietic stem cells. Immunization of C57BL/6 mice with MOG35-55 results in the acceleration of EAE development. Anti-DNA antibodies are usually directed against DNA–histone complexes resulting from cell apoptosis. During the acute EAE phase (7-20 days after immunization), catalytic antibodies efficiently hydrolysing myelin basic protein (MBP), MOG and DNA are produced with parallel suppression of antibodies hydrolysing histones. We could show that in contrast to MOG, immunization with histone-DNA results in a reduction of proteinuria, a significant increase in anti-DNA, anti-MBP and anti-MOG antibody titres, as well as an increase in their catalytic activities for antigen hydrolysis, but slightly changes the concentration of cytokines. Contrary to MOG, DNA–histone and DNA-met-BSA only stimulated the formation of anti-DNA antibodies hydrolysing DNA with a long delay (15-20 days after immunization). Our data indicate that for C57BL/6 mice immunization with DNA-met-BSA and DNA–histone complexes may have opposing effects compared to MOG. DNA–histone stimulates the appearance of histone-hydrolysing abzymes in the acute EAE phase, while abzymes with DNase activity appear at significantly later time-points. We conclude that MOG, DNA–histone and DNA-met-BSA have different effects on numerous bone marrow, cellular, immunological and biochemical parameters of immunized mice, but all antigens finally significantly stimulate the development of the EAE.
AB - Experimental autoimmune encephalomyelitis (EAE)-prone C57BL/6 mice are used as a model of human multiple sclerosis. We immunize mice with myelin oligodendrocyte glycoprotein (MOG), DNA–histone and DNA-methylated bovine serum albumin (met-BSA) complexes to reveal different characteristics of EAE development including bone marrow lymphocyte proliferation and differentiation profiles of hematopoietic stem cells. Immunization of C57BL/6 mice with MOG35-55 results in the acceleration of EAE development. Anti-DNA antibodies are usually directed against DNA–histone complexes resulting from cell apoptosis. During the acute EAE phase (7-20 days after immunization), catalytic antibodies efficiently hydrolysing myelin basic protein (MBP), MOG and DNA are produced with parallel suppression of antibodies hydrolysing histones. We could show that in contrast to MOG, immunization with histone-DNA results in a reduction of proteinuria, a significant increase in anti-DNA, anti-MBP and anti-MOG antibody titres, as well as an increase in their catalytic activities for antigen hydrolysis, but slightly changes the concentration of cytokines. Contrary to MOG, DNA–histone and DNA-met-BSA only stimulated the formation of anti-DNA antibodies hydrolysing DNA with a long delay (15-20 days after immunization). Our data indicate that for C57BL/6 mice immunization with DNA-met-BSA and DNA–histone complexes may have opposing effects compared to MOG. DNA–histone stimulates the appearance of histone-hydrolysing abzymes in the acute EAE phase, while abzymes with DNase activity appear at significantly later time-points. We conclude that MOG, DNA–histone and DNA-met-BSA have different effects on numerous bone marrow, cellular, immunological and biochemical parameters of immunized mice, but all antigens finally significantly stimulate the development of the EAE.
KW - C57BL/6 mice
KW - catalytic antibodies
KW - colony formation
KW - cytokines
KW - eae model
KW - hematopoietic progenitors differentiation
KW - immunization with DNA–histone complex
KW - SYSTEMIC-LUPUS-ERYTHEMATOSUS
KW - immunization with DNA-histone complex
KW - COLONY FORMATION
KW - MRL/MPJ-LPR MICE
KW - NECROSIS-FACTOR-ALPHA
KW - MYELIN BASIC-PROTEIN
KW - SUBCLASSES IGG1-IGG4
KW - HYDROLYZING ANTIBODIES
KW - MULTIPLE-SCLEROSIS
KW - AUTOIMMUNE-DISEASES
KW - CATALYTIC HETEROGENEITY
UR - http://www.scopus.com/inward/record.url?scp=85054068317&partnerID=8YFLogxK
U2 - 10.1111/jcmm.13850
DO - 10.1111/jcmm.13850
M3 - Article
C2 - 30265424
AN - SCOPUS:85054068317
VL - 22
SP - 5816
EP - 5832
JO - Journal of Cellular and Molecular Medicine
JF - Journal of Cellular and Molecular Medicine
SN - 1582-1838
IS - 12
ER -
ID: 16953337