白细胞介素-5在增强免疫豚鼠气道嗜酸性粒细胞迁移中的作用。

Role of interleukin-5 in enhanced migration of eosinophils from airways of immunized guinea-pigs.

作者信息

Coëffier E, Joseph D, Vargaftig B B

机构信息

Unité de Pharmacologie Cellulaire, Unité Associée Institut Pasteur-INSERM no. 285, Paris, France.

出版信息

Br J Pharmacol. 1994 Nov;113(3):749-56. doi: 10.1111/j.1476-5381.1994.tb17057.x.

DOI:10.1111/j.1476-5381.1994.tb17057.x

PMID:7858864

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1510407/

Abstract

Platelet activating factor (PAF), leukotriene B4 (LTB4) and interleukin-5 (IL-5) are potent chemoattractants for guinea-pig eosinophils, which may be involved in eosinophil recruitment and up-regulation in allergic diseases. Eosinophils from the bronchoalveolar lavage fluid (BALF) of ovalbumin-sensitized guinea-pigs were collected 24 h after antigen provocation and migration induced by PAF, LTB4 and rhIL-5 was studied. 2. Total BALF content and distribution of eosinophils were greater in immunized, ovalbumin-challenged guinea-pigs (5.0 +/- 0.8 x 10(6)/guinea-pig; 12 +/- 1%) than in immunized, saline-challenged animals (3.0 +/- 0.7 x 10(6)/guinea-pig; 7 +/- 1%). 3. The chemoattraction of eosinophils isolated on a metrizamide gradient was studied in micro-Boyden chambers, results being expressed as the number of migrating cells (mean +/- s.e. mean). PAF and LTB4-induced migration of eosinophils from immunized and OA-challenged guinea-pigs were significantly enhanced, as compared to immunized and saline-challenged animals (170 +/- 36 vs 35 +/- 9 migrating eosinophils for 10 nM PAF; 271 +/- 60 vs 110 +/- 19 for 1 nM LTB4). 4. The IL-5 antibody TRFK-5, in vivo, reduced eosinophil recruitment in BALF of antigen-challenged immunized animals as well as the enhanced responsiveness of eosinophils from the challenged animals, suggesting a role for IL-5 in the priming of eosinophils in vivo. 5. In contrast to TRFK-5, nedocromil sodium reduced to a similar extent eosinophil, macrophage and lymphocyte recruitment into the BALF of antigen-challenged, but failed to down-regulate the enhanced responsiveness of eosinophils from the challenged animals. 6. The increased eosinophil content in lungs from antigen-challenged guinea-pigs is thus selectively reduced by the anti-IL-5 antibody, which also attenuates the concomitant enhancement of the eosinophil responsiveness, supporting the concept that IL-5 is essential for recruitment and priming of eosinophils in vivo. In contrast, nedocromil sodium reduced non-selectively the total cell recruitment to the airways,but failed to attenuate the enhanced responsiveness of those eosinophils which migrated, indicating that its effects involve a different target.

摘要

血小板活化因子（PAF）、白三烯B4（LTB4）和白细胞介素-5（IL-5）是豚鼠嗜酸性粒细胞强有力的趋化因子，它们可能参与过敏性疾病中嗜酸性粒细胞的募集和上调过程。在抗原激发24小时后，收集卵清蛋白致敏豚鼠支气管肺泡灌洗液（BALF）中的嗜酸性粒细胞，并研究PAF、LTB4和重组人IL-5诱导的迁移情况。2. 免疫后经卵清蛋白激发的豚鼠BALF中嗜酸性粒细胞的总含量和分布（5.0±0.8×10⁶/只豚鼠；12±1%）高于免疫后经生理盐水激发的动物（3.0±0.7×10⁶/只豚鼠；7±1%）。3. 在微量Boyden小室中研究了在甲泛葡胺梯度上分离的嗜酸性粒细胞的趋化作用，结果以迁移细胞数（平均值±标准误）表示。与免疫后经生理盐水激发的动物相比，PAF和LTB4诱导免疫后经卵清蛋白激发的豚鼠嗜酸性粒细胞迁移显著增强（对于10 nM PAF，迁移的嗜酸性粒细胞数为170±36对35±9；对于1 nM LTB4，为271±60对110±19）。4. IL-5抗体TRFK-5在体内减少了抗原激发的免疫动物BALF中嗜酸性粒细胞的募集以及激发动物嗜酸性粒细胞增强的反应性，提示IL-5在体内嗜酸性粒细胞的启动中起作用。5. 与TRFK-5相反，奈多罗米钠在相似程度上减少了抗原激发动物BALF中嗜酸性粒细胞、巨噬细胞和淋巴细胞的募集，但未能下调激发动物嗜酸性粒细胞增强的反应性。6. 因此，抗IL-5抗体选择性地减少了抗原激发豚鼠肺中增加的嗜酸性粒细胞含量，这也减弱了嗜酸性粒细胞反应性的伴随增强，支持了IL-5在体内嗜酸性粒细胞募集和启动中必不可少的观点。相比之下，奈多罗米钠非选择性地减少了气道中总的细胞募集，但未能减弱迁移的嗜酸性粒细胞增强的反应性，表明其作用涉及不同的靶点。