Pediatric Rheumatology Online Journal → July 2003 → Vasculitides → Kawasaki Disease → Abstract #134

SUPERANTIGEN MEDIATED VASCULITIS: THE ROLE OF ENDOTHELIAL CELL ACTIVATION IN VESSEL REMODELLING

S. M. Benseler,¹ T. T. Duong,¹ E. D. Silverman,¹ R. S. M. Yeung.¹

Rheumatolgy, Cancer and Blood Research, The Hospital for Sick Children, Toronto, ON, Canada

Background: Superantigens have been shown to be important in the pathogenesis of Kawasaki disease. The functional role of endothelial cells as a potential target and translator of intravascular inflammation into aneurysm formation remains unclear.
Objective: To determine the role of endothelial cells in the pathogenesis of Lactobacillus casei wall extract (LCWE) induced Kawasaki vasculitis in mice.
Methods: Primary aortic and coronary endothelial cell (EC) cultures, peripheral blood lymphocytes, splenocytes, and aortic vessel explants of C57B1/6 and hHLA-DQ6 transgenic mice were obtained. EC activation was determined by fluorescence activated cell surface (FACS) analysis of activation marker PECAM/CD31. The capacity of vessel explants to support lymphocyte activation mediated by LCWE was examined using H3-Thymidine incorporation T-cell proliferation assays. Vessel-remodeling capacity of ECs was assayed by FACS analysis of VEGF-Receptor (VEGF-R) and TGFb-Receptor Endoglin (CD105) expression.
Results: LCWE induces EC-dependant lymphocyte proliferation after pre-incuation leading to an 5 fold increase in the H3-Thymidine uptake compared to unstimulated EC explants (13500±1460cpm, controls 2400± 342cpm) with a maximum at 4h LCWE incubation time. PECAM and VEGF-R expression on ECs is upregulated after LCWE incubation (PECAM: 31% versus 5%, VEGF-R: 18% versus 5%) compared to unstimulated ECs. VEGF-R expression has its maximun at 72h LCWE stimulation (29%± 4% versus 16% ± 6% in PBS controlls). CD105 expression, which has a high baseline level on ECs, is not significantly increased by LCWE (44% versus 51% at 48h LCWE).
Conclusion: Superantigen exposure of endothelial cells led to activation of both lymphocytes and ECs in LCWE induced Kawasaki vasculitis. Superantigen induces ECs to express both markers of activation and vessel remodelling. ECs are capable of translating superantigen induced intravascular inflammation into aneurysm formation. The role of smooth muscle cells in disease process needs to be determined.