TY - JOUR
T1 - Experimental autoimmune encephalomyelitis (EAE) in CCR2-/- mice
T2 - Susceptibility in multiple strains
AU - Gaupp, Stefanie
AU - Pitt, David
AU - Kuziel, William A.
AU - Cannella, Barbara
AU - Raine, Cedric S.
N1 - Funding Information:
Supported in part by Health and Human Services (HHS) grants NS 11920, NS 08952, and NS 07098 ; and National Multiple Sclerosis Society grant, RG 1001-J-10. C.S.R. is the Wollowick Family Professor in Multiple Sclerosis Research.
PY - 2003/1/1
Y1 - 2003/1/1
N2 - Chemokines are low molecular weight cytokines which act as chemoattractants for infiltrating cells bearing appropriate receptors (CCR) to sites of inflammation. It has been proposed that CCR2 on monocytes is responsible for their recruitment into the central nervous system (CNS) in experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis, and two previous reports have described resistance of CCR2-/- mice to EAE. The present study examined three different mouse strains with CCR2 deletions for susceptibility to EAE. Animals were studied up to 4 months post-sensitization and were examined by neuropathology, RNase protection assay, in situ hybridization, and in vitro assays. All three strains were found to be susceptible to EAE: C57BL/6 x J129 and Balb c strains, 100%; and C57BL/6, 67%. Unusual in CNS lesions of CCR2-/- mice was an overabundance of neutrophils versus monocytes in wild-type animals. An attempt of the immune system to develop compensatory mechanisms for the lack of CCR2 was evidenced by a corresponding increase in mRNA for other chemokines and CCR. Inasmuch as neutrophils replaced monocytes and led to demyelination, our findings support the concept that promiscuity of chemokines and CCR was able to surmount the deletion of CCR2, still resulting in full expression of this autoimmune disease.
AB - Chemokines are low molecular weight cytokines which act as chemoattractants for infiltrating cells bearing appropriate receptors (CCR) to sites of inflammation. It has been proposed that CCR2 on monocytes is responsible for their recruitment into the central nervous system (CNS) in experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis, and two previous reports have described resistance of CCR2-/- mice to EAE. The present study examined three different mouse strains with CCR2 deletions for susceptibility to EAE. Animals were studied up to 4 months post-sensitization and were examined by neuropathology, RNase protection assay, in situ hybridization, and in vitro assays. All three strains were found to be susceptible to EAE: C57BL/6 x J129 and Balb c strains, 100%; and C57BL/6, 67%. Unusual in CNS lesions of CCR2-/- mice was an overabundance of neutrophils versus monocytes in wild-type animals. An attempt of the immune system to develop compensatory mechanisms for the lack of CCR2 was evidenced by a corresponding increase in mRNA for other chemokines and CCR. Inasmuch as neutrophils replaced monocytes and led to demyelination, our findings support the concept that promiscuity of chemokines and CCR was able to surmount the deletion of CCR2, still resulting in full expression of this autoimmune disease.
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U2 - 10.1016/S0002-9440(10)63805-9
DO - 10.1016/S0002-9440(10)63805-9
M3 - Article
C2 - 12507897
AN - SCOPUS:0037221976
SN - 0002-9440
VL - 162
SP - 139
EP - 150
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 1
ER -