Short-term sPECAM-Fc treatment ameliorates EAE while chronic use hastens onset of symptoms.
The homophilic cell adhesion molecule PECAM-1 is a major participant in the migration of leukocytes across endothelium. We examined the ability of a chimeric soluble PECAM-1 fused to human IgG-Fc to impair leukocyte entry through the blood-brain barrier and reduce CNS autoimmunity. sPECAM-Fc impaired migration of lymphocytes across brain endothelial monolayers and diminished the severity of EAE, an experimental model of MS, when administered at the onset of symptoms. However, in mice transgenic for sPECAM-Fc, the chronically elevated levels of sPECAM-Fc hastened onset of EAE disease without significantly changing clinical score severity. Our data suggest that short-term treatment of diseases like MS with sPECAM-Fc has therapeutic potential.
Reinke
Emily K
EK
Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA.
Lee
Jangeun
J
Zozulya
Alla
A
Karman
Jozsef
J
Muller
William A
WA
Sandor
Matyas
M
Fabry
Zsuzsanna
Z
D000818:Animals; D001921:Brain / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics / Q000494:pharmacology; D066298:In Vitro Techniques; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D037342:Pertussis Toxin; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013997:Time Factors
D007074:Immunoglobulin G; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D037342:Pertussis Toxin