Expression of integrins in experimental autoimmune neuritis and Guillain-Barré syndrome.
Integrins are a subclass of adhesion molecules that mediate cell-cell and cell-extracellular matrix interactions. Integrins influence transendothelial migration of lymphocytes and monocytes and are suitable targets for experimental immunotherapy. They are critically involved in the pathogenesis of autoimmune neuritis and abnormally expressed in human neuropathies. Also, the role of integrins in myelination, neurite outgrowth, and nerve regeneration suggests that they could be involved in the recovery phase of immune-mediated neuropathies. We investigated by immunohistochemistry the expression of a number of integrin subunits during the course of experimental autoimmune neuritis (EAN). Results were compared with the human immune neuropathy Guillain-Barre syndrome (GBS) and extended in vitro. Inflammation and demyelination in both EAN and GBS induced the down-regulation of beta4 integrin in Schwann cells (SCs), whereas loss of alpha2 was noted only in EAN. When axonal loss was present, SCs displayed alpha5 integrin, in both EAN and GBS. In vitro, basal lamina and inflammatory cytokines modulated the expression of beta4 in SCs, but they did not influence alpha2 and alpha5 expression. Finally, integrins were differentially expressed in blood vessels during EAN. In conclusion, the spatiotemporal changes in integrin expression may be used to characterize, stage, and better understand the pathogenesis and evolution of inflammation during GBS and EAN. This may help to establish useful, novel therapy for immune-mediated neuropathies.
Previtali
S C
SC
Department of Neurology, Clinical Research Group for Multiple Sclerosis, Julius-Maximilians-Universität, Würzburg, Germany.
Archelos
J J
JJ
Hartung
H P
HP
D000818:Animals; D001808:Blood Vessels / Q000378:metabolism; D005260:Female; D007150:Immunohistochemistry; D016023:Integrins / Q000378:metabolism*; D009444:Neuritis, Autoimmune, Experimental / Q000378:metabolism*; D011129:Polyradiculoneuropathy / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D012016:Reference Values
D016023:Integrins