Expression of CC chemokines and their receptors in the eye in autoimmune anterior uveitis associated with EAE

G. Adamus, M. Manczak, M. Machnicki

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

PURPOSE. To determine the pattern of expression of CC chemokines and their receptors in the eyes of Lewis rats and to establish their role in autoimmune anterior uveitis (AU) associated with experimental autoimmune encephalomyelitis (EAE). METHODS. EAE/AU was induced in Lewis rats with myelin basic protein in complete Freund's adjuvant (CFA). The rats were scored for the development of clinical EAE and AU. The expression of CCL5/regulated on activation normal T-cell expressed and secreted (RANTES), CCL2/monocyte chemotactic protein (MCP)-1, CCL3/macrophage inflammatory protein (MIP)-1α, and CCL4/MIP-1β and their receptors was examined at the preclinical stage, onset, peak, and recovery by RT-PCR and ELISA. EAE/AU rats were treated with neutralizing polyclonal antibodies against CCL3/MIP-1α, CCL4/MIP-1β, CCL2/MCP-1, and CCL5/RANTES and tested for the suppression of onset of clinical AU and EAE. The control group received normal rabbit IgG at the same dose. RESULTS. The gene expression of those chemokines was upregulated concurrently with symptom onset of EAE/AU and correlated with the intensity of inflammatory changes in the eye and central nervous system (CNS). The highest expression of CCL4/RANTES, CCL2/MCP-1, and CCL3/MIP-1α in the eye was detected at onset of clinical uveitis, whereas CCL4/MIP-1β was elevated at the peak of AU. The expression of chemokine receptors associated with T-helper (Th)1-type response, CCR1 and CCR5, correlated with their appropriate ligands and was the highest at the peak of AU, whereas CCR2, the receptor for CCL2/MCP-1, was present before the onset of the disease. Treatment of anti-MIP-1β and anti-MCP-1 significantly delayed the onset and shortened the duration of AU and EAE. Anti-MIP-1α treatment had no effect on clinical EAE but inhibited the clinical signs of AU. Although CCL5/RANTES expression was observed during the entire course of the disease, anti-RANTES treatment had no effect on clinical disease progression. CONCLUSIONS. The data suggest that CCL2/MCP-1, CCL3/MIP-1α, and CCL4/MIP-β contribute to the recruitment of inflammatory cells into the eye and CNS and to disease activity.

Original languageEnglish (US)
Pages (from-to)2894-2903
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Volume42
Issue number12
StatePublished - Nov 17 2001

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Expression of CC chemokines and their receptors in the eye in autoimmune anterior uveitis associated with EAE'. Together they form a unique fingerprint.

  • Cite this