Altered vascular permeability and early onset of experimental autoimmune encephalomyelitis in PECAM-1–deficient mice
Donnasue Graesser, … , Britta Engelhardt, Joseph A. Madri
Donnasue Graesser, … , Britta Engelhardt, Joseph A. Madri
Published February 1, 2002
Citation Information: J Clin Invest. 2002;109(3):383-392. https://doi.org/10.1172/JCI13595.
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Article

Altered vascular permeability and early onset of experimental autoimmune encephalomyelitis in PECAM-1–deficient mice

Abstract

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.

Authors

Donnasue Graesser, Anna Solowiej, Monika Bruckner, Emily Osterweil, Amy Juedes, Sandra Davis, Nancy H. Ruddle, Britta Engelhardt, Joseph A. Madri

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PECAM-KO endothelial cells exhibit prolonged permeability changes in res...
PECAM-KO endothelial cells exhibit prolonged permeability changes in response to histamine exposure in vitro. Lung-derived PECAM-KO microvascular endothelial cells and lung-derived PECAM-KO microvascular endothelial cells transfected with and expressing WT PECAM-1 (PECAM-RC) were cultured in confluent monolayers on transwell membranes, and exposed to histamine. The permeability of the monolayers to Evans blue dye was measured by collecting media from the lower wells and measuring the absorbance at 650 nm. PECAM-KO endothelial cell monolayers (squares) exhibited prolonged permeability to the dye, lasting at least 20 minutes, while the PECAM-RC endothelial cell monolayers (diamonds) were impermeable to the dye by 15 minutes. n = 5.