Journal of Neuroimmunology, Vol. 128 (1-2) (2002) pp. 16-22
Masaru Matsui a, Jennifer Weaver a, Amanda E.I. Proudfoot b, Jerome R. Wujek a, Tao Wei a, Edward Richer a, Bruce D. Trapp a, Ashwin Rao a and Richard M. Ransohoff a,c
a Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
b Serono Pharmaceutical Research Institute, 14 Chemin des Aulx, 1228 Plan-les Ouates, Geneva, Switzerland
c Department of Neurology, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
Specific chemokines and chemokine receptors have been implicated in inflammatory demyelinating diseases of the central nervous system (CNS), including multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE).
Amino-terminal modifications of chemokines can alter receptor interactions, converting agonists to specific antagonists.
To examine the function in EAE of murine types 1 and 5 CC chemokine receptors (CCR1 and CCR5), we used Met-RANTES, a peptide that blocks both receptors; controls received heat-inactivated peptide.
There was no effect of active treatment on acute-monophasic EAE, regardless whether compound was given at onset or in a pre-treatment regimen.
Administered at disease onset, Met-RANTES modestly but significantly ameliorated fixed neurological disability at the endpoint of chronic-relapsing EAE.
Met-RANTES treatment did not reduce CNS cellular infiltrates or up-regulation of CCR1 and CCR5 in affected CNS tissues.
Analysis of a subset of mice suggested a trend towards reduced axonal pathology in those receiving active treatment.
These data indicate that chemokine receptor blockade with Met-RANTES does not affect leukocyte trafficking in chronic-relapsing EAE.
Further analysis of the effects of chemokine receptor blockade may need to focus on leukocyte activation within the affected CNS as well as trafficking events.
© 2002 Elsevier Science B.V.