Inhibition of lung inflammatory reactions in rats by an anti-human IL-8 antibody.
Inhibition of lung inflammatory reactions in rats by an anti-human IL-8 antibody.
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DOI：
10.4049/jimmunol.150.12.5585
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发表时间：
1993-06
影响因子：
4.4
通讯作者：
M. Mulligan;M. Jones;M. Bolanowski;M. Baganoff;C. L. Deppeler;D. M. Meyers;U. Ryan;P. Ward
中科院分区：
文献类型：
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作者：
M. Mulligan;M. Jones;M. Bolanowski;M. Baganoff;C. L. Deppeler;D. M. Meyers;U. Ryan;P. Ward
IL-8属于趋化细胞因子家族，可能在炎症反应中发挥重要作用。本研究发现一种抗人rIL-8的鼠单抗(DM/C7)对大鼠炎性肺损伤具有保护作用。DM/C7对细胞因子诱导的大鼠中性粒细胞趋化多肽无反应。在体内，DM/C7阻断了糖原诱导的中性粒细胞在大鼠体内的聚集，并对免疫复合物沉积后的肺和真皮血管损伤具有高度的保护作用。后一种损伤模型最近被证明是E-选择素依赖的。DM/C7的保护作用与减少中性粒细胞在组织中的积累有关，这是通过髓过氧化物酶含量来衡量的。DM/C7与肿瘤坏死因子-α刺激的大鼠肺动脉内皮细胞表达的表位以及肺内沉积免疫复合物后的肺血管内皮细胞反应。在Ig G免疫复合体诱导的肺损伤模型中，DM/C7的保护作用可被人rIL-8预先吸收抗体所消除。抗细胞因子诱导的中性粒细胞趋化多肽的多克隆抗体即使阻断了细胞因子诱导的中性粒细胞趋化因子的体外趋化活性，也不能保护免疫复合物诱导的血管损伤。在眼镜蛇蛇毒因子全身激活C所致快速发展的肺损伤模型中，DM/C7不具有保护作用。此外，在非中性粒细胞依赖的IgA免疫复合体诱导的肺损伤模型中，DM/C7的治疗不具有保护作用。这些数据表明，在炎症性肺损伤中，与E-选择素依赖的中性粒细胞在大鼠体内的募集有关，抗人IL-8的抗体也可以阻止中性粒细胞的募集，从而对肺损伤起到保护作用。这些数据表明，在这种肺损伤模型中存在一种类似IL-8的产物。
IL-8 belongs to the family of chemotactic cytokines and may play an important role in the inflammatory response. In the current studies, a murine mAb (DM/C7) to human rIL-8 was found to have protective effects in inflammatory lung injury in rats. DM/C7 was nonreactive with the rat cytokine-induced neutrophil chemoattractant peptide. In vivo, DM/C7 blocked the glycogen-induced accumulation of neutrophils in rats and was highly protective against lung and dermal vascular injury after deposition of IgG immune complexes. The latter model of injury has recently been shown to be E-selectin dependent. The protective effects of DM/C7 correlated with reduced tissue accumulation of neutrophils, as measured by myeloperoxidase content. DM/C7 reacted with an epitope expressed by TNF-alpha-stimulated rat pulmonary artery endothelial cells and with the pulmonary vascular endothelium after intrapulmonary deposition of IgG immune complexes. In the model of IgG immune complex-induced lung injury, the protective effects of DM/C7 were abolished by prior absorption of the antibody with human rIL-8. Polyclonal antibody to cytokine-induced neutrophil chemoattractant peptide failed to protect against IgG immune complex-induced vascular injury even though this antibody blocked the in vitro chemotactic activity of cytokine-induced neutrophil chemoattractant. In the model of rapidly developing lung injury due to systemic activation of C after infusion of cobra venom factor, DM/C7 was not protective. As well, in the neutrophil-independent model of IgA immune complex-induced lung injury, treatment with DM/C7 was not protective. These data indicate that in inflammatory lung injury that is linked to E-selectin-dependent recruitment of neutrophils in rats, antibody to human IL-8 also blocks recruitment of neutrophils and thereby affords protection against lung injury. The data suggest the presence of an IL-8-like product in this model of lung injury.