Brown Charles R, Blaho Victoria A, Loiacono Christie M
Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO 65211, USA.
J Immunol. 2003 Jul 15;171(2):893-901. doi: 10.4049/jimmunol.171.2.893.
The development of experimental Lyme arthritis has been correlated with the expression of a number of chemokines and cytokines, however, none of these have been measured directly from the arthritic joint. We examined the temporal expression of IL-1beta, IL-4, IL-6, IL-10, IL-12p70, GM-CSF, IFN-gamma, TNF-alpha, macrophage inflammatory protein-2, KC, macrophage inflammatory protein-1alpha, and monocyte chemoattractant protein-1 directly from the tibiotarsal joint in arthritis-resistant C57BL/6 (B6) and -susceptible C3H/He (C3H) mice. Only the chemokines KC and monocyte chemoattractant protein-1 were differentially expressed in joints of B6 and C3H mice and correlated with the development of Lyme arthritis. Infection of CXCR2(-/-) mice on either genetic background resulted in a significant decrease in the development of pathology, although infection of CCR2(-/-) mice had little or no effect. Neutrophils in CXCR2(-/-) mice were marginalized within blood vessels and could not enter the joint tissue. These results suggest that chemokine-mediated recruitment of neutrophils into the infected joint is a key requirement for the development of experimental Lyme arthritis.
实验性莱姆关节炎的发展与多种趋化因子和细胞因子的表达相关，然而，这些因子均未直接从关节炎关节中检测。我们直接检测了抗关节炎的C57BL/6（B6）小鼠和易感的C3H/He（C3H）小鼠胫跗关节中白细胞介素-1β（IL-1β）、白细胞介素-4（IL-4）、白细胞介素-6（IL-6）、白细胞介素-10（IL-10）、白细胞介素-12p70、粒细胞-巨噬细胞集落刺激因子（GM-CSF）、干扰素-γ（IFN-γ）、肿瘤坏死因子-α（TNF-α）、巨噬细胞炎性蛋白-2（MIP-2）、KC、巨噬细胞炎性蛋白-1α（MIP-1α）和单核细胞趋化蛋白-1（MCP-1）的时序表达。只有趋化因子KC和单核细胞趋化蛋白-1在B6和C3H小鼠的关节中差异表达，并与莱姆关节炎的发展相关。无论何种遗传背景，CXCR2基因敲除小鼠感染后病理发展均显著降低，而CCR2基因敲除小鼠感染后影响甚微或无影响。CXCR2基因敲除小鼠中的中性粒细胞在血管内边缘化，无法进入关节组织。这些结果表明，趋化因子介导的中性粒细胞向感染关节的募集是实验性莱姆关节炎发展的关键条件。
