In vivo blood monocyte migration to acute inflammatory reactions, IL-1 alpha, TNF-alpha, IFN-gamma, and C5a utilizes LFA-1, Mac-1, and VLA-4. The relative importance of each integrin.
In vivo blood monocyte migration to acute inflammatory reactions, IL-1 alpha, TNF-alpha, IFN-gamma, and C5a utilizes LFA-1, Mac-1, and VLA-4. The relative importance of each integrin.
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DOI：
10.4049/jimmunol.154.12.6533
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发表时间：
1995-06
影响因子：
4.4
通讯作者：
T. Issekutz
中科院分区：
文献类型：
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作者：
T. Issekutz
评价了单核细胞整合素Mac-1、LFA-1和VLA-4在体外对大鼠血液单核细胞与大鼠微血管内皮细胞粘附的作用以及这些受体在体内单核细胞迁移至炎症中的重要性。单核细胞粘附细胞因子（IL-1，IFN-γ，和TNF-α）刺激的内皮细胞介导的Mac-1，LFA-1，和VLA-4，但Mac-1似乎是不太重要的LFA-1或VLA-4。静脉注射后，大量的51铬标记的血液单核细胞迁移到2小时内由C5 a，IL-1 α，IFN-γ，TNF-α，LPS，和聚肌苷酸：胞苷酸诱导的皮肤炎症部位。抗Mac-1 mAb处理没有影响，而抗LFA-1抑制迁移到C5 a和细胞因子的20 - 40%。阻断Mac-1和LFA-1可使所有刺激物的单核细胞积累减少50 - 70%。抗VLA-4抑制单核细胞向IL-1 α、IFN-γ、TNF-α和LPS的迁移，但不抑制向C5 a的迁移。抗Mac-1抗体与抗VLA-4抗体的组合并没有增加这种抑制作用，而阻断VLA-4和LFA-1一起进一步抑制（60-85%）迁移。用针对所有三种整联蛋白的mAb的组合治疗抑制> 98%的单核细胞向炎性刺激物的迁移。结论：1）51 Cr血单核细胞可用于大鼠单核细胞向炎症反应迁移的定量研究。2)单核细胞使用Mac-1、LFA-1和VLA-4进行体外粘附和体内迁移至皮肤炎症，并且这些整合素对于正常迁移是必需的，因为阻断所有三种整合素几乎消除了单核细胞积累。3)Mac-1的作用不如LFA-1重要，因为LFA-1似乎取代了Mac-1，VLA-4和LFA-1可以介导大部分粘附和迁移。4)启动炎症刺激也修改单核细胞整合素的使用，支持白细胞外渗的多步骤组合模型。
UNLABELLED The role of the monocyte integrins, Mac-1, LFA-1, and VLA-4, on the adhesion of rat blood monocytes to rat microvascular endothelial cells in vitro and the importance of these receptors in monocyte migration to inflammation in vivo were evaluated. Monocyte adhesion to cytokine (IL-1, IFN-gamma, and TNF-alpha)-stimulated endothelial cells was mediated by Mac-1, LFA-1, and VLA-4, but Mac-1 appeared to be less important than LFA-1 or VLA-4. After i.v. injection, large numbers of 51Cr-labeled blood monocytes migrated within 2 h to dermal inflammatory sites induced by C5a, IL-1 alpha, IFN-gamma, TNF-alpha, LPS, and poly inosinic:cytidylic acid. Anti-Mac-1 mAb treatment had no effect, whereas anti-LFA-1 inhibited migration to C5a and the cytokines by 20 to 40%. Blocking both Mac-1 and LFA-1 decreased monocyte accumulation by 50 to 70% to all stimuli. Anti-VLA-4 inhibited monocyte migration to IL-1 alpha, IFN-gamma, TNF-alpha, and LPS, but not to C5a. Combining anti-Mac-1 with anti-VLA-4 did not increase this inhibition, whereas blocking VLA-4 and LFA-1 together further suppressed (60-85%) migration. Combined treatment with mAb to all three integrins inhibited > 98% of the monocyte migration to the inflammatory stimuli. IN CONCLUSION 1) 51Cr blood monocytes can be used to quantify monocyte migration to inflammatory reactions in the rat. 2) Monocytes use Mac-1, LFA-1, and VLA-4 for in vitro adhesion and in vivo migration to cutaneous inflammation, and these integrins are essential for normal migration because blockade of all three virtually abolishes monocyte accumulation. 3) Mac-1 plays a less important role than LFA-1, as LFA-1 appears to substitute for Mac-1, and VLA-4 and LFA-1 can mediate much of the adhesion and migration. 4) The initiating inflammatory stimulus also modifies monocyte integrin usage, supporting the multistep combinatorial model of leukocyte extravasation.