Altered M1/M2 activation patterns of monocytes in severe relapsing experimental rat model of multiple sclerosis. Amelioration of clinical status by M2 activated monocyte administration.
OBJECTIVE
We investigated proinflammatory M1 and immunomodulatory M2 activation profiles of circulating monocytes in relapsing experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis, and tested whether altered M1/M2 equilibrium promotes CNS inflammation.


RESULTS
Approaches of MRI macrophage tracking with USPIO nanoparticles and expression patterns of M1/M2 macrophages and microglia in brain and M1/M2 monocytes in blood samples at various disease stages revealed that M1/M2 equilibrium in blood and CNS favors mild EAE, while imbalance towards M1 promotes relapsing EAE. We consequently investigated whether M2 activated monocyte restoration in peripheral blood could cure acute clinical EAE disease. Administration of ex vivo activated M2 monocytes both suppressed ongoing severe EAE and increased immunomodulatory expression pattern in lesions, confirming their role in the induction of recovery.


CONCLUSIONS
We conclude that imbalance of monocyte activation profiles and impaired M2 expression, are key factors in development of relapses. Our study opens new perspectives for therapeutic applications in MS.
Mikita
Joanna
J
University Victor Segalen, France.
Dubourdieu-Cassagno
Nadège
N
Deloire
Mathilde Sa
MS
Vekris
Antoine
A
Biran
Marc
M
Raffard
Gérard
G
Brochet
Bruno
B
Canron
Marie-Hélène
MH
Franconi
Jean-Michel
JM
Boiziau
Claudine
C
Petry
Klaus G
KG
D000818:Animals; D001921:Brain / Q000098:blood supply / Q000276:immunology* / Q000473:pathology; D002478:Cells, Cultured; D003287:Contrast Media; D003911:Dextrans; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D005260:Female; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles; D009000:Monocytes / Q000201:enzymology / Q000276:immunology / Q000637:transplantation*; D009103:Multiple Sclerosis / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D052247:Nitric Oxide Synthase Type II / Q000097:blood; D051381:Rats; D012720:Severity of Illness Index; D013997:Time Factors
D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; C097921:ferumoxtran-10; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat