Cheraim Alessandra Bonacini, Xavier-Elsas Pedro, de Oliveira Sandra Helena Penha, Batistella Tiago, Russo Momtchilo, Gaspar-Elsas Maria Ignez, Cunha Fernando Queiroz
Departamento de Imunologia, Instituto de Microbiologia Prof. Paulo de Góes, UFRJ, Rio de Janeiro, Brazil.
Life Sci. 2008 Aug 1;83(5-6):214-22. doi: 10.1016/j.lfs.2008.06.004. Epub 2008 Jun 15.
Subcutaneous heat-coagulated egg white implants (EWI) induce chronic, intense local eosinophilia in mice, followed by asthma-like responses to airway ovalbumin challenge. Our goal was to define the mechanisms of selective eosinophil accumulation in the EWI model. EWI carriers were challenged i.p. with ovalbumin and the contributions of cellular immunity and inflammatory mediators to the resulting leukocyte accumulation were defined through cell transfer and pharmacological inhibition protocols. Eosinophil recruitment required Major Histocompatibility Complex Class II expression, and was abolished by the leukotriene B4 (LTB4) receptor antagonist CP 105.696, the 5-lipoxygenase inhibitor BWA4C and the 5-lipoxygenase activating protein inhibitor MK886. Eosinophil recruitment in EWI carriers followed transfer of: a) CD4+ (but not CD4-) cells, harvested from EWI donors and restimulated ex vivo; b) their cell-free supernatants, containing LTB4. Restimulation in the presence of MK886 was ineffective. CC chemokine receptor ligand (CCL)5 and CCL2 were induced by ovalbumin challenge in vivo. mRNA for CCL17 and CCL11 was induced in ovalbumin-restimulated CD4+ cells ex vivo. MK886 blocked induction of CCL17. Pretreatment of EWI carriers with MK886 eliminated the effectiveness of exogenously administered CCL11, CCL2 and CCL5. In conclusion, chemokine-producing, ovalbumin-restimulated CD4+ cells initiate eosinophil recruitment which is strictly dependent on LTB4 production.
皮下热凝卵清蛋白植入物（EWI）可在小鼠中诱发慢性、强烈的局部嗜酸性粒细胞增多，随后对气道卵清蛋白激发产生类似哮喘的反应。我们的目标是确定EWI模型中嗜酸性粒细胞选择性积聚的机制。给EWI携带者腹腔注射卵清蛋白，并通过细胞转移和药理学抑制方案确定细胞免疫和炎症介质对由此产生的白细胞积聚的作用。嗜酸性粒细胞募集需要主要组织相容性复合体II类表达，并且被白三烯B4（LTB4）受体拮抗剂CP 105.696、5-脂氧合酶抑制剂BWA4C和5-脂氧合酶激活蛋白抑制剂MK886消除。EWI携带者中的嗜酸性粒细胞募集在以下情况后发生转移：a）从EWI供体收获并在体外重新刺激的CD4+（而非CD4-）细胞；b）其无细胞上清液，含有LTB4。在MK886存在下的重新刺激无效。卵清蛋白在体内激发可诱导CC趋化因子受体配体（CCL）5和CCL2。在体外，卵清蛋白重新刺激的CD4+细胞中可诱导CCL17和CCL11的mRNA。MK886可阻断CCL17的诱导。用MK886预处理EWI携带者可消除外源性给予的CCL11、CCL2和CCL5的有效性。总之，产生趋化因子的、卵清蛋白重新刺激的CD4+细胞启动嗜酸性粒细胞募集，这严格依赖于LTB4的产生。
