Abstract
In multiple sclerosis and in its animal model experimental autoimmune encephalomyelitis (EAE), inflammatory cells migrate across the endothelial blood-brain barrier and gain access to the CNS. The involvement of P-selectin glycoprotein ligand 1 (PSGL-1) and of its major endothelial ligand P-selectin in this process have been controversial. In this study we demonstrate that although encephalitogenic T cells express functional PSGL-1, which can bind to soluble and immobilize P-selectin if presented in high concentrations, PSGL-1 is not involved T cell interaction with P-selectin expressing brain endothelial cells in vitro. Furthermore, neither anti-PSGL-1 Abs nor the lack of PSGL-1 in PSGL-1-deficient mice inhibits the recruitment of inflammatory cells across the blood-brain barrier or the development of clinical EAE. Taken together, our findings demonstrate that PSGL-1 is not required for the pathogenesis of EAE.
Highlights
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During EAE immunostaining for P-selectin glycoprotein ligand 1 (PSGL-1) was observed on the majority of inflammatory cells localized within perivascular cuffs (Fig. 1A)
In this study we show that encephalitogenic T lymphocytes display surface expression of PSGL-1, their PSGL-1-mediated binding to P-selectin is apparently poor as it was only observed when P-selectin was available at high concentration or density
Summary
BBB, blood-brain barrier; PSGL, P-selectin glycoprotein ligand; EAE, experimental autoimmune encephalomyelitis; tEAE, transferred EAE; PLP, proteolipid protein; MOG, myelin oligodendrocytic glycoprotein; PMN, polymorphonuclear granulocyte. Activated integrins mediate the firm adhesion of the leukocytes to the vascular endothelium by binding to their endothelial ligands, which belong to the Ig superfamily. This leads to the extravasation of the leukocyte. ␣4 integrins in the initial capture and the firm adhesion of autoaggressive T cells within the spinal cord white matter microvasculature [11]. These apparent discrepancies prompted us to investigate the functional expression of the homodimeric sialomucin PSGL-1 on encephalitogenic T cells and its potential involvement in inflammatory cell recruitment across the BBB during EAE. PSGL-1 is not required for the development of EAE in SJL or C57BL/6 mice
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