In vivo monitoring of macrophage infiltration in experimental autoimmune neuritis by magnetic resonance imaging.
We report on the in vivo assessment of macrophage infiltration in adoptive transfer experimental autoimmune neuritis (AT-EAN), a prototypic Th-1-mediated autoimmune disorder of the peripheral nervous system (PNS). Lewis rats received systemic injections of superparamagnetic iron oxide (SPIO) particles at days 2, 3, 4, 5, or 9 after adoptive transfer of P2-specific T-cells and were scanned by standard 1.5 T magnetic resonance imaging (MRI) always 24 h later. MRI revealed focal signal loss of the cauda equina indicating iron accumulation in spinal nerves already at the preclinical stage (day 3). Signal loss peaked at day 4, when first clinical signs developed. At the maximum of clinical disease, signal loss already declined and disappeared on days 6 and 10. In spinal nerve sections, Perl's iron stain showed focal cellular accumulation of SPIO at days 3, 4, and 5 in ED1-positive macrophages. Spinal nerves at days 6 and 10 exhibited massive macrophage infiltrates, but no more iron deposition. In conclusion, SPIO-enhanced MRI provides a novel in vivo tool to assess the timing of macrophage entry into target tissues during an immunopathologic attack and holds promise to monitor immunotherapeutic interventions.
Stoll
Guido
G
Department of Neurology, Julius-Maximilians Universität, Josef-Schneider-Str. 11, D-97080, Würzburg, Germany. stoll_g@klinik.uni-wuerzburg.de
Wesemeier
Carmen
C
Gold
Ralf
R
Solymosi
Laszlo
L
Toyka
Klaus V
KV
Bendszus
Martin
M
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002420:Cauda Equina / Q000473:pathology; D002465:Cell Movement; D053331:Ectodysplasins; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000473:pathology*; D005260:Female; D005290:Ferric Compounds; D052203:Ferrosoferric Oxide; D007150:Immunohistochemistry / Q000379:methods; D007501:Iron / Q000378:metabolism; D008264:Macrophages / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008565:Membrane Proteins / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D013997:Time Factors
D053331:Ectodysplasins; D005290:Ferric Compounds; D008565:Membrane Proteins; C427127:superparamagnetic blood pool agent; D007501:Iron; D052203:Ferrosoferric Oxide