Chemokines and peripheral nerve demyelination.
It has been speculated that beta-chemokines play a pivotal role in the development of peripheral nervous system (PNS) disorders characterized by mononuclear cell infiltration. In experimental allergic neuritis (EAN), an animal model for human Guillain-Barré syndrome (GBS) with mononuclear cell infiltration, we found by quantitative PCR that beta-chemokine messages were upregulated during the active stage. Moreover, an increase in the monocyte chemoattractant protein-1 (MCP-1) message was found in the preclinical stage of EAN, suggesting the critical role of MCP-1 for inducing mononuclear cell infiltrations in this model. Since many cell lineages other than immune cells can produce chemokines, this early upregulation of MCP-1 may be mediated by non-immune cells, probably endothelia or Schwann cells. To date, apart from MCP-1, only RANTES (Regulated on activation, normal T cell expressed and secreted) and macrophage inflammatory protein (MIP)-1alpha have been examined in EAN and found to have similar kinetics of induction. Therefore, understanding the regulation of production of these chemokines as well as mechanisms of inhibiting chemokine/receptor interactions in the PNS may ultimately lead to disease-specific therapy for GBS and related demyelinating disorders.
Fujioka
T
T
Department of Neurology, University of Pennsylvania Medical School, Philadelphia 19104, USA.
Kolson
D L
DL
Rostami
A M
AM
D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D019742:Chemokines, CC / Q000378:metabolism; D003711:Demyelinating Diseases / Q000209:etiology* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D009444:Neuritis, Autoimmune, Experimental / Q000378:metabolism*; D010523:Peripheral Nervous System Diseases / Q000209:etiology* / Q000378:metabolism; D011129:Polyradiculoneuropathy / Q000209:etiology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D012583:Schwann Cells / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation / Q000502:physiology
D018932:Chemokine CCL2; D018925:Chemokines; D019742:Chemokines, CC; D012333:RNA, Messenger