The correlation between severity of paraparesis and reduced density of resident antigen-presenting cells implicates an unknown role for the spinal perivascular macrophages in experimental autoimmune encephalomyelitis in rats.
To study alterations in the morphology of spinal perivascular macrophages (SPM) during experimental allergic encephalomyelitis (EAE), we labelled SPM by intracerebroventricular (i.c.v.) injection of horseradish peroxidase (HRP). As earlier electron microscopical analysis had shown severely damaged SPM, we suspected that each inflammatory process is accompanied by the death of SPM. To prove this hypothesis, we compared the numerical density of resident SPM (i.c.v. labelled in red by Fluoro-Ruby) with that of monocytes/macrophages recruited to the perivascular space (i.c.v. labelled in green by Fluoro-Emerald). At the peak of paraparesis, the density of resident SPM was reduced by 33%. Since this reduction contrasted sharply with earlier data indicating a massive increase in the density of SPM during EAE, we checked our findings after general or selective suppression of the immune response to myelin autoantigens with the drugs dexamethasone and copaxone, respectively. Dexamethasone treatment commenced after evident paraparesis accelerated recovery, but did not influence SPM density. Immunisation with copaxone completely prevented the occurrence of EAE (monitored by video-based motion analysis of tail motility); the subsequent histological analysis revealed no reduction in SPM density. Based on this inverse correlation between the severity of EAE and the density of resident macrophages, we conclude that SPM plays an important role in the pathogenesis of EAE.
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D002452:Cell Count; D002465:Cell Movement / Q000276:immunology; D003907:Dexamethasone / Q000008:administration & dosage; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000097:blood / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D005456:Fluorescent Dyes / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D020335:Paraparesis / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D011917:Rats, Inbred Lew; D012720:Severity of Illness Index; D013116:Spinal Cord / Q000098:blood supply* / Q000276:immunology / Q000473:pathology*; D013623:Tail / Q000502:physiology; D013997:Time Factors
D005456:Fluorescent Dyes; D003907:Dexamethasone