Gao J X, Issekutz A C, Issekutz T B
Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada.
J Immunol. 1994 Dec 15;153(12):5689-97.
We have previously found that polymorphonuclear leukocyte (PMNL) migration to adjuvant arthritic joints of rats was only partially inhibited by mAbs to the adhesion molecules LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18), suggesting that there is a CD11/CD18-independent mechanism for PMNL migration to inflamed joints. Adjuvant arthritis in rats is believed to be initiated by a T lymphocyte-dependent immune response and maintained by proinflammatory cytokines such as IL-1 and TNF-alpha. Here we studied two types of joint inflammation: that induced by a delayed-type hypersensitivity (DTH) reaction in the joint and that induced by intra-articular (i.a.) injection of cytokines, to explore PMNL migration to inflamed joints and examine the role of CD18. 51Cr-labeled blood PMNL were used to measure PMNL migration in rats to inflammatory reactions in joints and compared with reactions in skin. A large number of PMNL migrated to the carpal and talar joints after i.a. injection of Mycobacterium purified protein derivative in sensitized animals to induce DTH, but there was minimal PMNL migration to this DTH reaction in the skin. This migration to the joints was not inhibited by mAbs to LFA-1 alone or mAbs to LFA-1 plus Mac-1 that almost completely inhibited PMNL accumulation in dermal inflammatory reactions induced by zymosan-activated serum (C5adesArg), endotoxin, IL-1 alpha, or TNF-alpha in the same rats. Intra-articular injection of the cytokines IL-1 alpha and TNF-alpha, but not IFN-gamma, induced marked PMNL accumulation in the joints; this was strongly inhibited by the treatment of rats with anti-LFA-1 and anti-Mac-1. Thus, PMNL migrate to DTH induced in joints but not in skin, and this migration is CD18-independent, but migration to i.a. IL-1 alpha and TNF-alpha is largely CD18 dependent in both joints and skin. This suggests that both the joint microenvironment and the T cell dependence of the inflammatory reaction in the joint governs the mechanism of PMNL recruitment.
我们先前发现，针对黏附分子淋巴细胞功能相关抗原-1（LFA-1，CD11a/CD18）和巨噬细胞抗原-1（Mac-1，CD11b/CD18）的单克隆抗体仅部分抑制多形核白细胞（PMNL）向大鼠佐剂性关节炎关节的迁移，这表明存在一种不依赖CD11/CD18的PMNL向炎症关节迁移的机制。大鼠佐剂性关节炎被认为由T淋巴细胞依赖性免疫反应引发，并由促炎细胞因子如白细胞介素-1（IL-1）和肿瘤坏死因子-α（TNF-α）维持。在此，我们研究了两种类型的关节炎症：关节中迟发型超敏反应（DTH）诱导的炎症以及关节内（i.a.）注射细胞因子诱导的炎症，以探究PMNL向炎症关节的迁移并检验CD18的作用。用51Cr标记的血液PMNL来测量大鼠中PMNL向关节炎症反应的迁移，并与皮肤中的反应进行比较。在致敏动物中关节内注射结核分枝杆菌纯化蛋白衍生物以诱导DTH后，大量PMNL迁移至腕关节和距骨关节，但在皮肤中该DTH反应几乎没有PMNL迁移。向关节的这种迁移不受单独针对LFA-1的单克隆抗体或针对LFA-1加Mac-1的单克隆抗体的抑制，而这些单克隆抗体几乎完全抑制了相同大鼠中由酵母聚糖激活血清（C5adesArg）、内毒素、IL-1α或TNF-α诱导的皮肤炎症反应中的PMNL聚集。关节内注射细胞因子IL-1α和TNF-α而非干扰素-γ（IFN-γ）可诱导关节中显著的PMNL聚集；用抗LFA-1和抗Mac-1处理大鼠可强烈抑制这种聚集。因此，PMNL迁移至关节中诱导的DTH而非皮肤中的DTH，且这种迁移不依赖CD18，但向关节内IL-1α和TNF-α的迁移在关节和皮肤中很大程度上依赖CD18。这表明关节微环境以及关节中炎症反应的T细胞依赖性均决定了PMNL募集的机制。
