BORRELIA-BURGDORFERI AND INTERLEUKIN-1 PROMOTE THE TRANSENDOTHELIAL MIGRATION OF MONOCYTES IN-VITRO BY DIFFERENT MECHANISMS

A prominent feature of Lyme disease is the perivascular accumulation o f mononuclear leukocytes, Incubation of human umbilical vein endotheli al cells (HUVEC) cultured on amniotic tissue with either interleukin-l (IL-1) or Borrelia burgdorferi, the spirochetal agent of Lyme disease , increased the rate at which human monocytes migrated across the endo thelial monolayers. Very late antigen 4 (VLA-4) and CD11/CD18 integrin s mediated migration of monocytes across HUVEC exposed to either B. bu rgdorferi or IL-1 in similar manners. Neutralizing antibodies to the c hemokine monocyte chemoattractant protein 1 (MCP-1) inhibited the migr ation of monocytes across unstimulated, IL-l-treated, or B. burgdorfer i-stimulated HUVEC by 91% +/- 3%, 65% +/- 2%, or 25% +/- 22%, respecti vely. Stimulation of HUVEC with B. burgdorferi also promoted a 6 fold +/- 2-fold increase in the migration of human CD4(+) T lymphocytes. Al though MCP-1 played only a limited role in the migration of monocytes across B, burgdorferi-treated HUVEC, migration of CD4(+) T lymphocytes across HUVEC exposed to spirochetes was highly dependent on this chem okine, The anti-inflammatory cytokine IL-10 reduced both migration of monocytes and endothelial production of MCP-1 in response to B. burgdo rferi by approximately 50%, yet IL-10 inhibited neither migration nor secretion of MCP-1 when HUVEC were stimulated with IL-1. Our results s uggest that activation of endothelium by B. burgdorferi may contribute to formation of the chronic inflammatory infiltrates associated with Lyme disease. The transendothelial migration of monocytes that is indu ced by B, burgdorferi is significantly less dependent on MCP-1 than is migration induced by IL 1. Selective inhibition by IL-IO further indi cates that B. burgdorferi and IL 1 employ distinct mechanisms to activ ate endothelial cells.