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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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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Challenged vessel permeability is altered in PECAM-KO mice. (a) PIs of m...
Challenged vessel permeability is altered in PECAM-KO mice. (a) PIs of mouse brain tissue after induction of EAE. In the PECAM-KO mice, there was a significant increase (twofold) in PI by day 6 after immunization, and the vessels remained permeable for a longer period of time compared with those of WT mice (n = 3, P < 0.03). (b) Skin vessel PI was not affected during EAE in either group of mice (n = 3). (c) PIs in mouse skin following dermal histamine challenge. The vessels of the PECAM-KO mice remained markedly permeable to dye for up to 10 minutes after histamine injection, while the vessels of the WT mice are mostly impermeable to the dye by 10 minutes. PIs for both groups return to base line by 15 minutes after histamine injection (n = 3). (d) Due to the longer time period that the PECAM-KO vessels remain “leaky” following dermal histamine challenge, more dye accumulates in the skin tissue of the PECAM-KO mice by 15 minutes following histamine challenge than in that of WT mice (n = 3, *P = 0.039). S/P, status post.