Nagata M, Yamamoto H, Tabe K, Sakamoto Y, Matsuo H
Pulmonary Division, Second Department of Internal Medicine, Saitama Medical School, Saitama, Japan.
Int Arch Allergy Immunol. 2000 May;122 Suppl 1:15-9. doi: 10.1159/000053625.
The initial step of eosinophil accumulation in allergic inflammation is adhesion of circulating eosinophils to vascular endothelial cells (EC). There is evidence that the adhesive property of circulating eosinophils is upregulated following antigen exposure. Although the exact mechanism remains to be established, cytokine(s) produced by antigen-stimulated mononuclear cells is (are) likely key factor(s).
The objective of this study was to examine the factor(s) responsible for eosinophil adhesion and migration induced by the antigen-stimulated mononuclear cells obtained from atopic asthmatics.
Peripheral blood mononuclear cells (PBMC) isolated from house-dust-mite-sensitive bronchial asthmatics were cultured for 96 h in the presence or absence of 1 microg/ml Dermatophagoides farinae (Df) antigen. Eosinophils were isolated from peripheral blood of healthy subjects. Eosinophil-adhesion-inducing activity in the culture supernatants of PBMC was examined by the ability to modify the adhesion of eosinophils to human pulmonary microvascular endothelial cells (HPMEC) in the presence or absence of anti-cytokine/chemokine antibodies. Eosinophil migration induced by the supernatants was also examined.
Eosinophil adhesion to HPMEC was significantly augmented by the supernatants of Df-stimulated PBMC, which was significantly inhibited by anti-GM-CSF, but not by anti-IL-5, anti-RANTES, or isotype-matched controls. On the other hand, eosinophil migration induced by the supernatants was inhibited by anti-GM-CSF and partly by anti-RANTES.
Both eosinophil adhesion and migration induced by the antigen-stimulated PBMC involve GM-CSF. In contrast, RANTES is involved only in the eosinophil migration. These molecules may participate in the development of eosinophil accumulation at the allergic inflammation sites.
嗜酸性粒细胞在过敏性炎症中聚集的初始步骤是循环中的嗜酸性粒细胞与血管内皮细胞（EC）黏附。有证据表明，抗原暴露后循环嗜酸性粒细胞的黏附特性会上调。尽管确切机制尚待确定，但抗原刺激的单核细胞产生的细胞因子可能是关键因素。
本研究的目的是检测来自特应性哮喘患者的抗原刺激单核细胞诱导嗜酸性粒细胞黏附和迁移的因素。
从对屋尘螨敏感的支气管哮喘患者中分离出外周血单核细胞（PBMC），在存在或不存在1微克/毫升粉尘螨（Df）抗原的情况下培养96小时。从健康受试者的外周血中分离嗜酸性粒细胞。通过在存在或不存在抗细胞因子/趋化因子抗体的情况下改变嗜酸性粒细胞与人肺微血管内皮细胞（HPMEC）黏附的能力，检测PBMC培养上清液中的嗜酸性粒细胞黏附诱导活性。还检测了上清液诱导的嗜酸性粒细胞迁移。
Df刺激的PBMC上清液显著增强了嗜酸性粒细胞对HPMEC的黏附，抗GM-CSF可显著抑制这种黏附，而抗IL-5、抗RANTES或同型对照则无此作用。另一方面，上清液诱导的嗜酸性粒细胞迁移受到抗GM-CSF的抑制，部分受到抗RANTES的抑制。
抗原刺激的PBMC诱导的嗜酸性粒细胞黏附和迁移均涉及GM-CSF。相比之下，RANTES仅参与嗜酸性粒细胞迁移。这些分子可能参与了嗜酸性粒细胞在过敏性炎症部位的聚集过程。
