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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Figure 2

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Antigen-specific T lymphocytes derived from PECAM-KO and WT mice are ind...
Antigen-specific T lymphocytes derived from PECAM-KO and WT mice are indistinguishable in in vitro priming assays (a) and in vivo adoptive transfer (b) and marrow engraftment assays (c). (a) In vitro priming assay illustrating that the proliferation of in vivo MOG peptide–primed T lymphocytes harvested from the draining lymph nodes of PECAM-KO and WT mice is indistinguishable. n = 5. Vertical lines represent standard deviations. (b) Adoptive transfer study illustrating that the time of onset of EAE correlates with the presence or absence of endothelial PECAM-1. KO → WT = antigen-specific PECAM-1–deficient T lymphocytes adoptively transferred into a WT recipient. WT → KO = antigen-specific PECAM-1–positive T lymphocytes adoptively transferred into a PECAM-1–deficient recipient. KO → KO = antigen-specific PECAM-1–deficient T lymphocytes adoptively transferred into a PECAM-1–deficient recipient. n = 4. (c) PECAM-KO mice engrafted with WT marrow precursors (WT → KO), but not WT mice engrafted with PECAM-KO marrow precursors (KO → WT), exhibit an early incidence of EAE. This study also illustrates that the time of onset of EAE correlates with the presence or absence of endothelial PECAM-1. This graph represents an average of one of three independent experiments, each having groups of three WT → KO and KO → WT mice.