CCL2 and CCL5 mediate leukocyte adhesion in experimental autoimmune encephalomyelitis--an intravital microscopy study.
Experimental autoimmune encephalomyelitis (EAE) models multiple sclerosis (MS) and is characterized by marked mononuclear cell influx in the brain. Several studies have demonstrated a role for chemokines during EAE. It remains to be determined whether these mediators modulate EAE primarily by mediating leukocyte influx into the CNS or by modifying lymphocyte activation and/or trafficking into lymphoid organs. After induction of EAE with MOG(35-55), leukocyte recruitment peaked on day 14 and correlated with symptom onset, TNF-alpha production and production of CCL2 and CCL5. Levels of CXCL-10 and CCL3 were not different from control animals. Using intravital microscopy, we demonstrated that leukocyte rolling and adhesion also peaked at day 14. Treatment with anti-CCL2 or anti-CCL5 antibodies just prior to the intravital microscopy prevented leukocyte adhesion, but not rolling. Our data suggest that induction of leukocyte adhesion to the brain microvasculature is an important mechanism by which CCL2 and CCL5 participate in the pathophysiology of EAE.
dos Santos
Adriana Carvalho
AC
Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Barsante
Michele Mendes
MM
Arantes
Rosa Maria Esteves
RM
Bernard
Claude C A
CC
Teixeira
Mauro Martins
MM
Carvalho-Tavares
Juliana
J
D000704:Analysis of Variance; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D018932:Chemokine CCL2 / Q000276:immunology / Q000378:metabolism*; D018946:Chemokine CCL5 / Q000378:metabolism; D019742:Chemokines, CC / Q000276:immunology / Q000378:metabolism*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation / Q000473:pathology; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000378:metabolism; D013997:Time Factors
D000906:Antibodies; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D019742:Chemokines, CC; D006023:Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55)