J Clin Invest 2002 Feb;109(3):383-92
Graesser D, Solowiej A, Bruckner M, Osterweil E, Juedes A, Davis S, Ruddle NH, Engelhardt B, Madri JA.
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA. Max-Planck-Institute, Bad Nauheim, Germany. Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA.
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.