Chemokine expression by central nervous system resident cells and infiltrating neutrophils during experimental autoimmune encephalomyelitis in the BALB/c mouse.
The active role of chemokines in the central nervous system (CNS) during the pathogenesis of experimental autoimmune encephalomyelitis (EAE) has been clearly established. In this study the expression pattern of several chemokines and cytokines was elucidated using reverse transcription-PCR and immunohistochemistry in a recently established EAE model of the BALB/c mouse that is characterized by CNS infiltration of polymorphonuclear neutrophils. Elevated mRNA levels of the chemokines MIP-1alpha, MIP-2 and MCP-1 were detected in the CNS of diseased mice, whereas no chemokine expression could be measured in asymptomatic mice. Activated astrocytes were shown to be the main source of MIP-1alpha and MIP-2 before and during cellular CNS infiltration. Among the infiltrating immune cells the neutrophils secreted MIP-1alpha and MCP-1. These results suggest involvement of ordered chemokine expression during the process of neutrophil attraction into the CNS, which may play an important role in the initiation and perpetuation of autoimmune CNS inflammation in the BALB/c mouse. This is the first EAE model to describe CNS expression of the C-X-C chemokine MIP-2, corresponding to an observed neutrophil accumulation in the CNS.
Department of Biochemistry and Pharmacy, Abo Akademi University, and Turku Immunology Center, Finland. pnygarda@abo.fi
P T
PT
Nygårdas
J A
JA
Määttä
A E
AE
Hinkkanen
D000818:Animals; D002490:Central Nervous System / Q000166:cytology*; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics*; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D054426:Chemokine CXCL2; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D015870:Gene Expression; D007371:Interferon-gamma / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D015846:Monokines / Q000096:biosynthesis / Q000235:genetics*; D020556:Neutrophil Infiltration / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D054426:Chemokine CXCL2; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma