Burns M J, Furie M B
Department of Pathology, School of Medicine, State University of New York at Stony Brook, Stony Brook, New York 11794, USA.
Infect Immun. 1998 Oct;66(10):4875-83. doi: 10.1128/IAI.66.10.4875-4883.1998.
A prominent feature of Lyme disease is the perivascular accumulation of mononuclear leukocytes. Incubation of human umbilical vein endothelial cells (HUVEC) cultured on amniotic tissue with either interleukin-1 (IL-1) or Borrelia burgdorferi, the spirochetal agent of Lyme disease, increased the rate at which human monocytes migrated across the endothelial monolayers. Very late antigen 4 (VLA-4) and CD11/CD18 integrins mediated migration of monocytes across HUVEC exposed to either B. burgdorferi or IL-1 in similar manners. Neutralizing antibodies to the chemokine monocyte chemoattractant protein 1 (MCP-1) inhibited the migration of monocytes across unstimulated, IL-1-treated, or B. burgdorferi-stimulated HUVEC by 91% +/- 3%, 65% +/- 2%, or 25% +/- 22%, respectively. Stimulation of HUVEC with B. burgdorferi also promoted a 6-fold +/- 2-fold increase in the migration of human CD4(+) T lymphocytes. Although 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 chemokine. The anti-inflammatory cytokine IL-10 reduced both migration of monocytes and endothelial production of MCP-1 in response to B. burgdorferi by approximately 50%, yet IL-10 inhibited neither migration nor secretion of MCP-1 when HUVEC were stimulated with IL-1. Our results suggest 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 induced by B. burgdorferi is significantly less dependent on MCP-1 than is migration induced by IL-1. Selective inhibition by IL-10 further indicates that B. burgdorferi and IL-1 employ distinct mechanisms to activate endothelial cells.
莱姆病的一个显著特征是单核白细胞在血管周围积聚。将培养在羊膜组织上的人脐静脉内皮细胞（HUVEC）与白细胞介素-1（IL-1）或莱姆病的螺旋体病原体伯氏疏螺旋体一起孵育，会增加人单核细胞穿过内皮单层的迁移速率。极迟抗原4（VLA-4）和CD11/CD18整合素以相似的方式介导单核细胞穿过暴露于伯氏疏螺旋体或IL-1的HUVEC的迁移。针对趋化因子单核细胞趋化蛋白1（MCP-1）的中和抗体分别抑制单核细胞穿过未刺激的、IL-1处理的或伯氏疏螺旋体刺激的HUVEC的迁移，抑制率分别为91%±3%、65%±2%或25%±22%。用伯氏疏螺旋体刺激HUVEC也会使人类CD4(+) T淋巴细胞的迁移增加6倍±2倍。尽管MCP-1在单核细胞穿过伯氏疏螺旋体处理的HUVEC的迁移中仅起有限作用，但CD4(+) T淋巴细胞穿过暴露于螺旋体的HUVEC的迁移高度依赖于这种趋化因子。抗炎细胞因子IL-10使单核细胞的迁移以及内皮细胞对伯氏疏螺旋体反应产生MCP-1的量均减少约50%，然而当用IL-1刺激HUVEC时，IL-10既不抑制迁移也不抑制MCP-1的分泌。我们的结果表明，伯氏疏螺旋体激活内皮细胞可能有助于形成与莱姆病相关的慢性炎性浸润。伯氏疏螺旋体诱导的单核细胞跨内皮迁移对MCP-1的依赖性明显低于IL-1诱导的迁移。IL-10的选择性抑制进一步表明，伯氏疏螺旋体和IL-1采用不同的机制激活内皮细胞。
