Collins P D, Marleau S, Griffiths-Johnson D A, Jose P J, Williams T J
Department of Applied Pharmacology, National Heart and Lung Institute, London, United Kingdom.
J Exp Med. 1995 Oct 1;182(4):1169-74. doi: 10.1084/jem.182.4.1169.
Experiments were designed to study the effect of systemically administered IL-5 on local eosinophil accumulation induced by the intradermal injection of the chemokine eotaxin in the guinea pig. Intravenous interleukin-5 (IL-5) stimulated a rapid and dramatic increase in the numbers of accumulating eosinophils induced by i.d.-injected eotaxin and, for comparison, leukotriene B4. The numbers of locally accumulating eosinophils correlated directly with a rapid increase in circulating eosinophils: circulating eosinophil numbers were 13-fold higher 1 h after intravenous IL-5 (18.3 pmol/kg). This increase in circulating cells corresponded with a reduction in the number of displaceable eosinophils recovered after flushing out the femur bone marrow cavity. Intradermal IL-5, at the doses tested, did not induce significant eosinophil accumulation. We propose that these experiments simulate important early features of the tissue response to local allergen exposure in a sensitized individual, with eosinophil chemoattractant chemokines having an important local role in eosinophil recruitment from blood microvessels, and IL-5 facilitating this process by acting remotely as a hormone to stimulate the release into the circulation of a rapidly mobilizable pool of bone marrow eosinophils. This action of IL-5 would be complementary to the other established activities of IL-5 that operate over a longer time course.
设计实验以研究全身给予白细胞介素-5(IL-5)对豚鼠皮内注射趋化因子嗜酸性粒细胞趋化蛋白-1(eotaxin)诱导的局部嗜酸性粒细胞聚集的影响。静脉注射白细胞介素-5(IL-5)可刺激皮内注射eotaxin以及作为对照的白三烯B4诱导的聚集嗜酸性粒细胞数量迅速且显著增加。局部聚集的嗜酸性粒细胞数量与循环嗜酸性粒细胞的快速增加直接相关:静脉注射IL-5(18.3 pmol/kg)1小时后,循环嗜酸性粒细胞数量增加了13倍。循环细胞的这种增加与冲洗股骨骨髓腔后回收的可置换嗜酸性粒细胞数量减少相对应。在所测试的剂量下,皮内注射IL-5未诱导显著的嗜酸性粒细胞聚集。我们认为,这些实验模拟了致敏个体对局部过敏原暴露的组织反应的重要早期特征,嗜酸性粒细胞趋化趋化因子在从血液微血管募集嗜酸性粒细胞方面具有重要的局部作用,而IL-5通过作为一种激素远程起作用,刺激可快速动员的骨髓嗜酸性粒细胞池释放到循环中,从而促进这一过程。IL-5的这一作用将与IL-5在较长时间过程中发挥作用的其他既定活性相辅相成。