Crucial role of CCL3/MIP-1alpha in the recurrence of autoimmune anterior uveitis induced with myelin basic protein in Lewis rats.
In this study, we examined the role of CCL2/MCP-1, CCL3/MIP-1alpha, CCL4/MIP-1beta, and CCL5/RANTES during recurrent anterior uveitis (RAU). LEW rats injected with myelin basic protein (MBP) developed experimental autoimmune encephalomyelitis (EAE) and associated anterior uveitis (AU), which was mediated by CD4(+) T cells. After recovery, rats become resistant to EAE but developed RAU. Rats reinjected with MBP developed RAU without EAE. The chemokines tested were detected in the eye at RAU accelerated onset, increased as the disease progressed, and fell as clinical signs improved. At the same time, in the spinal cords of rats, these chemokines were still detected but at reduced levels. Administration of anti-MIP-1alpha neutralizing antibodies resulted in almost complete suppression of clinical RAU and significant reduction of inflammatory cell recruitment into the iris. Anti-MIP-1beta and anti-MCP-1 antibodies were effective in suppression of RAU but to lesser degree. Treatment with anti-RANTES antibodies was not effective in protecting against the recurrent development of the disease. In the eyes, the message for CCR1 and CCR5 was considerably elevated prior to the onset of AU and decreased after treatment with anti-chemokine antibodies. Our results suggest a crucial role of CCL3/MIP-1alpha in the development of RAU in Lewis rats. In addition, CCL2/MCP-1 and CCL4/MIP-1beta may also play a role in immunopathogenesis of RAU.
Manczak
Maria
M
Neurological Sciences Institute, Oregon Health & Science University, Portland, Oregon 97006, USA.
Jiang
Shuguang
S
Orzechowska
Beata
B
Adamus
Grazyna
G
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D018932:Chemokine CCL2 / Q000235:genetics / Q000276:immunology; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000235:genetics / Q000276:immunology; D005123:Eye / Q000276:immunology; D005260:Female; D019402:Macrophage Inflammatory Proteins / Q000235:genetics* / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D014606:Uveitis, Anterior / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics / Q000276:immunology
D000906:Antibodies; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019402:Macrophage Inflammatory Proteins