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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Figure 1

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PECAM-KO mice exhibit early incidence of EAE and earlier mononuclear cel...
PECAM-KO mice exhibit early incidence of EAE and earlier mononuclear cell infiltration of CNS parenchyma. (a) Average disease scores of WT and PECAM-KO mice calculated daily following induction of disease with MOG peptide. Disease symptoms manifested earlier in the PECAM-KO mice than in WT mice. (b–j) Representative hematoxylin and eosin–stained sections of cerebral cortex taken from the brains of WT (b, d, f, and h) and PECAM-KO mice (c, e, g, i, and j) at 4 days (b and c), 8 days (d and e), and 20 days (f–j) following EAE induction. PECAM-KO animals exhibited more intense perivascular (i) and parenchymal (j) infiltrates than their WT counterparts (h), which correlated with the difference in clinical disease scores noted at this time (a). Arrows indicate perivascular mononuclear cells. V, vessel; M, meninges. Scale bar = 50 μm.