Issekutz T B
Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada.
J Immunol. 1990 Mar 15;144(6):2140-6.
The first step in the migration of lymphocytes out of the blood is adherence of lymphocytes to endothelial cells (EC) in the postcapillary venule. It is thought that in inflammatory reactions cytokines activate the endothelium to promote lymphocyte adherence and migration into the inflammatory site. Injection of IFN-gamma, IFN-alpha/beta, and TNF-alpha into the skin of rats stimulated the migration of small peritoneal exudate lymphocytes (sPEL) into the injection site, and these cytokines mediated lymphocyte recruitment to delayed-type hypersensitivity, sites of virus injection, and in part to LPS. The effect of cytokines on lymphocyte adherence to rat microvascular EC was examined. IFN-gamma, IFN-alpha/beta, IL-1, TNF-alpha, and TNF-beta increased the binding of small peritoneal exudate lymphocyte (sPEL) to EC. IFN-gamma was more effective and stimulated adherence at much lower concentrations than the other cytokines. IL-2 did not increase lymphocyte adherence. LPS strongly stimulated lymphocyte binding. Treatment of EC, but not sPEL, enhanced adhesion, and 24 h of treatment with IFN-gamma and IL-1 induced near maximal adhesion. Lymph node lymphocytes, which migrate poorly to inflammatory sites, adhered poorly to unstimulated and stimulated EC, whereas sPEL demonstrated significant spontaneous adhesion which was markedly increased by IFN-gamma, IL-1, and LPS. Spleen lymphocytes showed an intermediate pattern of adherence. Combinations of IFN-gamma and TNF-alpha were additive in stimulating sPEL-EC adhesion. Depletion of sPEL and spleen T cells by adherence to IFN-gamma stimulated EC decreased the in vivo migration of the lymphocytes to skin sites injected with IFN-gamma, IFN-alpha/beta, TNF-alpha, poly I:C, LPS, and to delayed-type hypersensitivity reactions by 50%, and significantly increased the migration of these cells to normal lymph nodes, as compared to unfractionated lymphocytes. Thus the cytokines and lymphocytes involved in migration to cutaneous inflammation in the rat stimulate lymphocyte adhesion to rat EC in vitro, and IFN-gamma stimulated EC appear to promote the selective adhesion of inflammatory site-seeking lymphocytes.
淋巴细胞从血液中迁移出来的第一步是淋巴细胞与毛细血管后微静脉中的内皮细胞（EC）黏附。据认为，在炎症反应中，细胞因子激活内皮细胞，以促进淋巴细胞黏附并迁移到炎症部位。向大鼠皮肤注射干扰素-γ、干扰素-α/β和肿瘤坏死因子-α可刺激小腹腔渗出淋巴细胞（sPEL）迁移到注射部位，并且这些细胞因子介导淋巴细胞募集至迟发型超敏反应部位、病毒注射部位，部分介导至脂多糖部位。研究了细胞因子对淋巴细胞与大鼠微血管内皮细胞黏附的影响。干扰素-γ、干扰素-α/β、白细胞介素-1、肿瘤坏死因子-α和肿瘤坏死因子-β增加了小腹腔渗出淋巴细胞（sPEL）与内皮细胞的结合。干扰素-γ比其他细胞因子更有效，并且在比其他细胞因子低得多的浓度下就能刺激黏附。白细胞介素-2不会增加淋巴细胞黏附。脂多糖强烈刺激淋巴细胞结合。对内皮细胞而非sPEL进行处理可增强黏附，用干扰素-γ和白细胞介素-1处理24小时可诱导接近最大程度的黏附。迁移到炎症部位能力较差的淋巴结淋巴细胞，对未刺激和刺激后的内皮细胞黏附能力也较差，而sPEL表现出显著的自发黏附，这种黏附在干扰素-γ、白细胞介素-1和脂多糖作用下明显增加。脾淋巴细胞表现出中等程度的黏附模式。干扰素-γ和肿瘤坏死因子-α联合使用在刺激sPEL-内皮细胞黏附方面具有相加作用。通过黏附于干扰素-γ刺激的内皮细胞而耗尽sPEL和脾T细胞，可使淋巴细胞在体内向注射了干扰素-γ、干扰素-α/β、肿瘤坏死因子-α、聚肌胞苷酸、脂多糖的皮肤部位以及迟发型超敏反应部位的迁移减少50%，并且与未分级的淋巴细胞相比，显著增加了这些细胞向正常淋巴结的迁移。因此，参与大鼠皮肤炎症迁移的细胞因子和淋巴细胞在体外刺激淋巴细胞与大鼠内皮细胞黏附，并且干扰素-γ刺激的内皮细胞似乎促进了寻找炎症部位的淋巴细胞的选择性黏附。
