G. Adamus et al., Expression of CC chemokines and their receptors in the eye in autoimmune anterior uveitis associated with EAE, INV OPHTH V, 42(12), 2001, pp. 2894-2903
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 autoimmu
ne anterior uveitis (AU) associated with experimental autoimmune encephalom
yelitis (EAE).
METHODS. EAE/AU was induced in Lewis rats with myelin basic protein in comp
lete Freund's adjuvant (CFA). The rats were scored for the development of c
linical EAE and AU. The expression of CCL5/regulated on activation normal T
-cell expressed and secreted (RANTES), CCL2/monocyte chemotactic protein (M
CP)-1, CCL3/macrophage inflammatory protein (MIP)-1 alpha, and CCL4/MIP-1 b
eta and their receptors was examined at the preclinical stage. onset, peak,
and recovery by RT-PCR and ELISA. EAE/AU rats were treated with neutralizi
ng polyclonal antibodies against CCL3/MIP-1 alpha, CCL4/MIP-1 beta, CCL2/MC
P-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 up-regulated concurren
tly with symptom onset of EAE/AU and correlated with the intensity of infla
mmatory changes in the eye and central nervous system (CNS). The highest ex
pression of CCL4/RANTES, CCL2/MCP-1, and CCL3/MIP-1 alpha in the eye was de
tected at onset of clinical uveitis, whereas CCL4/MIP-1 beta was elevated a
t the peak of AU. The expression of chemokine receptors associated with T-h
elper (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 a
nti-MIP-1 beta and anti-MCP-1 significantly delayed the onset and shortened
the duration of AU and EAE. Anti-MIP-1 alpha treatment had no effect on cl
inical EAE but inhibited the clinical signs of AU. Although CCL5/RANTES exp
ression was observed during the entire course of the disease, anti-RANTES t
reatment had no effect on clinical disease progression.
CONCLUSIONS. The data suggest that CCL2/MCP-1, CCL3/MIP-1 alpha, and CCL4/M
IP-beta contribute to the recruitment of inflammatory cells into the eve an
d CNS and to disease activity.