Issekutz A C, Issekutz T B
Department of Pediatrics and Microbiology Dalhousie University, Halifax, Nova Scotia.
Lab Invest. 1991 May;64(5):656-63.
Infiltration of polymorphonuclear leukocytes (PMNL) and lymphocytes into joints is a prominent feature of human and experimental arthritis. Here we evaluated the usefulness of techniques previously employed for measuring blood PMNL and small, inflammatory site-seeking T-lymphocytes, used in models of dermal inflammation, to monitor the migration of these leukocytes into the joints of rats with adjuvant arthritis. One week after immunization of rats with adjuvant (Mycobacterium butyricum in oil), 51Cr-labeled rat blood PMNL migrated into the hind- and forelimb joints, 5- to 7-fold more than in control animals. This preceded 111In-labeled lymphocyte accumulation, plasma 125I-labeled albumin extravasation, and clinical disease by 4 to 6 days. At 2 weeks, PMNL accumulation in joints increased further, and T-lymphocyte accumulation increased to 6 times that in control animals. PMNL localization in joints maximized at 3 weeks, reaching 20 to 35 times that in control animals; T-lymphocyte accumulation plateaued between 2 and 3 weeks; and all parameters tended to decline by 4 weeks. Migration of T lymphocytes to lymph nodes and to skin inflammatory sites was normal, whereas PMNL migration to zymosan activated serum (C5adesArg) was increased in rats with adjuvant arthritis. Treatment of arthritic rats with dexamethasone (1 mg/kg for 2 to 3 days) caused a dramatic inhibition of plasma albumin extravasation and PMNL migration into arthritic joints and improved clinical scores. In contrast, small T-lymphocyte migration into the joints or into lymph nodes was not inhibited even though lymphocyte migration in the same animals into dermal inflammatory reactions induced by interferon gamma, tumor necrosis factor-alpha, endotoxin, and polyinosine-cytosine was markedly suppressed. These results indicate distinctive patterns of lymphocyte migration into arthritic joint inflammation as compared with dermal inflammation. The experiments demonstrate that the radiolabeled PMNL and lymphocyte migration assays employed here are sensitive and reproducible and allow simultaneous quantitation of leukocyte infiltration during arthritis. These techniques should be useful for studies of the mechanisms involved in leukocyte migration in arthritis and the modulation of joint inflammation.
多形核白细胞（PMNL）和淋巴细胞浸润关节是人类和实验性关节炎的一个显著特征。在此，我们评估了先前用于测量血液中PMNL和在皮肤炎症模型中使用的、寻找炎症部位的小型T淋巴细胞的技术，以监测这些白细胞向佐剂性关节炎大鼠关节的迁移情况。在用佐剂（油中的丁酸分枝杆菌）免疫大鼠一周后，51Cr标记的大鼠血液PMNL迁移至后肢和前肢关节，比对照动物多5至7倍。这比111In标记的淋巴细胞积聚、血浆125I标记的白蛋白外渗以及临床疾病提前4至6天出现。在2周时，关节中PMNL的积聚进一步增加，T淋巴细胞积聚增加至对照动物的6倍。关节中PMNL的定位在3周时达到最大值，为对照动物的20至35倍；T淋巴细胞积聚在2至3周之间达到平台期；到4周时所有参数都趋于下降。T淋巴细胞向淋巴结和皮肤炎症部位的迁移正常，而在佐剂性关节炎大鼠中，PMNL向酵母聚糖激活血清（C5adesArg）的迁移增加。用地塞米松（1 mg/kg，持续2至3天）治疗关节炎大鼠可显著抑制血浆白蛋白外渗和PMNL向关节炎关节的迁移，并改善临床评分。相比之下，小型T淋巴细胞向关节或淋巴结的迁移并未受到抑制，尽管同一动物中淋巴细胞向由干扰素γ、肿瘤坏死因子-α、内毒素和聚肌苷酸-胞嘧啶诱导的皮肤炎症反应中的迁移受到明显抑制。这些结果表明，与皮肤炎症相比，淋巴细胞向关节炎关节炎症的迁移模式具有独特性。实验表明，此处采用的放射性标记PMNL和淋巴细胞迁移测定法灵敏且可重复，能够同时定量关节炎期间白细胞的浸润情况。这些技术对于研究关节炎中白细胞迁移的机制以及关节炎症的调节应是有用的。
