BORRELIA-BURGDORFERI UP-REGULATES EXPRESSION OF ADHESION MOLECULES ONENDOTHELIAL-CELLS AND PROMOTES TRANSENDOTHELIAL MIGRATION OF NEUTROPHILS IN-VITRO

The accumulation of leukocytic infiltrates in perivascular tissues is a key step in the pathogenesis of Lyme disease, a chronic inflammatory disorder caused by Borrelia burgdorferi. During an inflammatory respo nse, endothelial cell adhesion molecules mediate the attachment of cir culating leukocytes to the blood vessel wall and their subsequent extr avasation into perivascular tissues. Using cultured human umbilical ve in endothelial cells (HUVEC) in a whole-cell enzyme-linked immunosorbe nt assay, we demonstrated that B. burgdorferi activated endothelium in a dose- and time-dependent fashion as measured by upregulation of the adhesion molecules E-selectin, vascular cell adhesion molecule 1 (VCA M-1), and intercellular adhesion molecule 1 (ICAM-1). As few as one sp irochete per endothelial cell stimulated increased expression of these molecules. Expression of E-selectin peaked after spirochetes and HUVE C were coincubated for 4 h and returned to near-basal levels by 24 h. In contrast, expression of VCAM-1 and ICAM-1 peaked at 12 h and remain ed elevated at 24 h. HUVEC monolayers cultured on acellular amniotic t issue were used to investigate the consequences of endothelial cell ac tivation by spirochetes. After incubation of HUVEC-amnion cultures wit h B. burgdorferi, subsequently added neutrophils migrated across the e ndothelial monolayers. This process was mediated by E-selectin and by CD11/CD18 leukocytic integrins. The extent of migration depended on bo th the number of spirochetes used to stimulate the HUVEC and the lengt h of the coincubation period. These results raise the possibility that B. burgdorferi induces a host inflammatory response and accompanying perivascular damage through activation of vascular endothelium.