Altered vascular permeability and early onset of experimental autoimmune encephalomyelitis in PECAM-1-deficient mice.
Platelet/endothelial cell adhesion molecule-1 (PECAM-1, CD31), a 130-kDa glycoprotein member of the Ig superfamily of transmembrane proteins, is expressed on endothelial cells, platelets, and subsets of leukocytes. It functions as a cell adhesion molecule as well as a scaffolding molecule capable of modulating cellular signaling pathways. In this study, using PECAM-1-deficient (KO) mice, as well as cells derived from these mice, we demonstrate that the absence of PECAM-1 expression is associated with an early onset of clinical symptoms during experimental autoimmune encephalomyelitis (EAE), a mouse model for the human autoimmune disease multiple sclerosis. During EAE, mononuclear cell extravasation and infiltration of the CNS occur at earlier time points in PECAM-KO mice than in wild-type mice. In vitro, T lymphocyte transendothelial migration across PECAM-KO endothelial cells is enhanced, regardless of expression of PECAM-1 on transmigrating T cells. Additionally, cultured PECAM-KO endothelial cells exhibit prolonged permeability changes in response to histamine treatment compared with PECAM-1-reconstituted endothelial cells. Lastly, we demonstrate an exaggerated and prolonged CNS vascular permeability during the development of EAE and a delay in restoration of dermal vascular integrity following histamine challenge in PECAM-KO mice.
Graesser
Donnasue
D
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA.
Solowiej
Anna
A
Bruckner
Monika
M
Osterweil
Emily
E
Juedes
Amy
A
Davis
Sandra
S
Ruddle
Nancy H
NH
Engelhardt
Britta
B
Madri
Joseph A
JA
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology*; D002465:Cell Movement; D002490:Central Nervous System / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000473:pathology; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology
D019408:Platelet Endothelial Cell Adhesion Molecule-1; D006632:Histamine