Expression of ICAM-1, VCAM-1, L-selectin, and leukosialin in the mouse central nervous system during the induction and remission stages of experimental allergic encephalomyelitis.
Adhesion molecules facilitate infiltration of leukocytes into the central nervous system (CNS) of mice with experimental allergic encephalomyelitis (EAE). Expression of the adhesion molecules ICAM-1 (CD54), VCAM-1 (CD106), L-selectin (CD62L), and leukosialin (CD43) was analyzed via immunocytochemistry 4-28 days after the injection of encephalitogen into EAE-susceptible SWXJ mice. Constitutive ICAM-1 expression on large-diameter CNS vessels was upregulated on post-injection days 8, 11, 14 and 18 (concurrent with de novo expression on smaller capillaries and glial cells), partially downregulated by day 23, and back to control levels by day 28. Constitutive VCAM-1 expression was upregulated by day 14 and back to control levels by day 28. Upregulation of ICAM-1 temporally coincided with the immigration of CD4+ lymphocytes and L-selectin+ leukocytes into the CNS, while downregulation coincided with their emigration. The infiltration of CD43+ leukocytes also coincided with the upregulation of vascular adhesion molecules, but CD43+ cells remained in the CNS after ICAM-1 and VCAM-1 had returned to control levels. Cellular infiltration and adhesion-molecule expression preceded EAE clinical symptoms by a minimum of 3 days, suggesting a causal role of adhesion molecules in the initiation of CNS inflammation. However, prophylactic injections of monoclonal antibodies against either ICAM-1, L-selectin, or CD43, did not ameliorate the clinical severity of EAE in this model.
Dopp
J M
JM
Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, NY 14642.
Breneman
S M
SM
Olschowka
J A
JA
D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002490:Central Nervous System / Q000378:metabolism*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005260:Female; D007150:Immunohistochemistry / Q000379:methods; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D019041:L-Selectin; D051917:Leukosialin; D008297:Male; D051379:Mice; D051381:Rats; D011919:Rats, Inbred Strains; D012795:Sialoglycoproteins / Q000378:metabolism*; D013194:Staining and Labeling; D019010:Vascular Cell Adhesion Molecule-1
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D051917:Leukosialin; D012795:Sialoglycoproteins; C497863:Spn protein, mouse; C497864:Spn protein, rat; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin