Nagata M, Yamamoto H, Shibasaki M, Sakamoto Y, Matsuo H
Pulmonary Division, Second Department of Internal Medicine, Saitama Medical School, Saitama, Japan.
Immunology. 2000 Nov;101(3):412-8. doi: 10.1046/j.1365-2567.2000.00123.x.
During eosinophil (EOS) accumulation at sites of allergic inflammation, an initial step is the binding of EOS to adhesion molecules expressed on vascular endothelial cells (EC). We have previously observed that adhesion of peripheral blood EOS to recombinant human vascular cell adhesion molecule-1 (rh-VCAM-1) stimulates the respiratory burst of EOS. Although the biological consequence of this activation remains to be elucidated, reactive oxygen species such as hydrogen peroxide (H2O2) may modify the adhesive property of EOS. In the present study, we examined whether H2O2 modifies the adhesive property of EOS. EOS were isolated from the peripheral blood of healthy subjects. Adhesion of the EOS to paraformaldehyde-fixed human umbilical vein EC (HUVEC), stimulated or not stimulated with tumour necrosis factor-alpha (TNF-alpha; 100 pM for 24 hr), was examined in the presence or absence of H2O2. H2O2 significantly enhanced adhesion of EOS to both resting and TNF-alpha-stimulated fixed HUVEC (P < 0.01, respectively). Such enhancing effects were inhibited by anti-beta2 integrin antibody or anti-CD11b antibody, but not by anti-CD11a or anti-alpha4 integrin antibody. H2O2 also enhanced EOS adhesion to rh-intracellular cell adhesion molecule-1 (ICAM-1) but not to rh-VCAM-1. Finally, H2O2 enhanced the expression of both CD11b and CD18 on EOS. These results indicate that H2O2 directly augments the adhesive property of EOS through beta2 integrin.
在嗜酸性粒细胞（EOS）在过敏性炎症部位积聚的过程中，第一步是EOS与血管内皮细胞（EC）上表达的黏附分子结合。我们之前观察到外周血EOS与重组人血管细胞黏附分子-1（rh-VCAM-1）的黏附会刺激EOS的呼吸爆发。尽管这种激活的生物学后果仍有待阐明，但诸如过氧化氢（H2O2）等活性氧可能会改变EOS的黏附特性。在本研究中，我们检测了H2O2是否会改变EOS的黏附特性。从健康受试者的外周血中分离出EOS。在有或没有H2O2的情况下，检测EOS对经或未经肿瘤坏死因子-α（TNF-α；100 pM，处理24小时）刺激的多聚甲醛固定的人脐静脉内皮细胞（HUVEC）的黏附情况。H2O2显著增强了EOS对静止和TNF-α刺激的固定HUVEC的黏附（P分别<0.01）。这种增强作用被抗β2整合素抗体或抗CD11b抗体抑制，但不被抗CD11a或抗α4整合素抗体抑制。H2O2还增强了EOS对重组细胞间黏附分子-1（ICAM-1）的黏附，但对rh-VCAM-1没有增强作用。最后，H2O2增强了EOS上CD11b和CD18的表达。这些结果表明，H2O2通过β2整合素直接增强了EOS的黏附特性。
