Table 1.

Potential routes of endothelial cell activation in SLE.

Cause of endothelial activation	Model	Findings
Environmental mediators	BBB disruption by treatment with LPS or epinephrine, in models of infection and stress, respectively (19, 81)	Treatment with human lupus serum containing anti-NMDAR antibodies following BBB disruption results in IgG deposition, hippocampal neuron loss, and memory impairment (LPS), or amygdala neuron loss and altered fear responses (epinephrine)
AECAs	In vitro treatment of HUVEC with anti- thrombomodulin (83, 84) or anti-NR2 antibodies (85)	Increased IL-6 and IL-8 expression
Complement	Mouse brain endothelial cells and MRL/lpr mice (63, 92)	C5aR activation yields increased CCL2 and CXCL2, NFκB signaling, and decreased ZO expression
Cytokine and chemokines	MRL/lpr mice (74) and CSF from human lupus patients (97)	Elevated ICAM-1 and VCAM-1 in MRL/lpr CNS; increased IL-6, IL-8, and MMP-9 in lupus CSF
TWEAK	In vitro hCMEC/D3 cells (5)	Elevated ICAM-1, CCL2, IL-6, IL-8, and MMP-9, ZO-1 degradation and decreased occludin levels