Issekutz A C, Issekutz T B
Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada.
J Immunol. 1993 Aug 15;151(4):2105-15.
Monocytes migrate from the blood into acute inflammatory reactions, where they differentiate into macrophages, and after 12 to 24 h become the predominant histologic feature of the inflammatory infiltrate. The quantitation of monocyte migration into these reactions has been difficult. This report employs a novel combination of techniques to isolate highly purified monocytes from the blood of rats, and shows that these cells have a normal t1/2 of 26 h and migrate efficiently after i.v. injection into cutaneous acute inflammatory sites. Monocytes labeled with 51Cr accumulated in delayed-type hypersensitivity reactions, and sites injected with killed Escherichia coli, LPS, poly-inosine: cytosine, zymosan-activated serum (ZAS), a source of C5adesArg, and the cytokines IL-1 alpha, TNF-alpha, and IFN-gamma. Both radiolabeled monocytes and neutrophils migrated rapidly to E. coli, LPS, ZAS, IL-1 alpha, and TNF-alpha with a large increase in cell accumulation by 2 h. Neutrophil migration declined rapidly to undetectable levels by 3 to 4 h to all five stimuli, and monocyte migration to ZAS and IL-1 alpha also declined by this time. In contrast, E. coli, LPS, and TNF-alpha caused a sustained migration of monocytes for 5 to 6 h, long after neutrophils had stopped accumulating. Intradermal IFN-gamma did not recruit neutrophils but stimulated a prolonged monocyte migration from 1 to 6 h. Combinations of LPS, TNF-alpha, and IFN-gamma synergistically enhanced the late (> 5 h) but not the early phase of monocyte recruitment. In conclusion, purified monocytes isolated from rat blood can be used to quantify monocyte migration in vivo, and these cells migrate rapidly to cutaneous inflammation and in response to chemotactic factors, IL-1 alpha, TNF-alpha, and IFN-gamma, with initial kinetics similar to those of neutrophils. However, monocyte-selective mechanisms are induced by IFN-gamma and also appear to be involved in prolonged monocyte migration to TNF-alpha, LPS, and E. coli.
单核细胞从血液迁移至急性炎症反应部位，在那里它们分化为巨噬细胞，并在12至24小时后成为炎症浸润的主要组织学特征。对单核细胞向这些反应部位迁移进行定量分析一直很困难。本报告采用了一种新颖的技术组合，从大鼠血液中分离出高度纯化的单核细胞，并表明这些细胞的正常半衰期为26小时，静脉注射后能有效地迁移至皮肤急性炎症部位。用51Cr标记的单核细胞在迟发型超敏反应部位以及注射了死大肠杆菌、脂多糖、聚肌苷酸:胞嘧啶、酵母聚糖激活血清（ZAS，一种C5adesArg来源）以及细胞因子白细胞介素-1α、肿瘤坏死因子-α和干扰素-γ的部位聚集。放射性标记的单核细胞和中性粒细胞都迅速迁移至大肠杆菌、脂多糖、ZAS、白细胞介素-1α和肿瘤坏死因子-α，2小时时细胞聚集大幅增加。对所有五种刺激物，中性粒细胞迁移在3至4小时迅速降至无法检测的水平，此时单核细胞向ZAS和白细胞介素-1α的迁移也下降。相比之下，大肠杆菌、脂多糖和肿瘤坏死因子-α在中性粒细胞停止聚集很久之后，仍能使单核细胞持续迁移5至6小时。皮内注射干扰素-γ不会募集中性粒细胞，但能刺激单核细胞从1至6小时持续迁移。脂多糖、肿瘤坏死因子-α和干扰素-γ的组合协同增强了单核细胞募集的晚期（>5小时）阶段，但对早期阶段无增强作用。总之，从大鼠血液中分离出的纯化单核细胞可用于体内定量单核细胞迁移，这些细胞能迅速迁移至皮肤炎症部位并对趋化因子、白细胞介素-1α、肿瘤坏死因子-α和干扰素-γ作出反应，其初始动力学与中性粒细胞相似。然而，干扰素-γ诱导了单核细胞选择性机制，并且似乎也参与了单核细胞向肿瘤坏死因子-α、脂多糖和大肠杆菌的长期迁移。
