Hirasawa Hiroyuki, Chiba Takahito, Ueki Shigeharu, Kamada Yumiko, Ito Wataru, Takeda Masahide, Fujita Miyoshi, Kato Hikari, Kayaba Hiroyuki, Chihara Junichi
Department of Clinical and Laboratory Medicine, Akita University School of Medicine, Akita, Japan.
Int Arch Allergy Immunol. 2008;146 Suppl 1:11-5. doi: 10.1159/000126054. Epub 2008 May 27.
Accumulation and activation of eosinophils in tissue are critical events in the allergic inflammatory response and adhesion molecules play important roles in this process. We previously demonstrated that human eosinophils expressed a nuclear receptor, peroxisome proliferator-activated receptor gamma (PPARgamma), and that stimulation with a PPARgamma agonist attenuated cytokine/chemokine-induced eosinophil activation, such as survival, chemotaxis and degranulation. In the present study, we investigated the effect of troglitazone, a synthetic PPARgamma agonist, on adherence to intercellular adhesion molecule-1 (ICAM-1). Eosinophils were purified from human peripheral blood, and the functional adherence to recombinant soluble ICAM-1-coated plates was examined. We found that in the presence of eotaxin, troglitazone inhibited eosinophil adherence in a concentration-dependent manner. This novel activity appears to be associated with modulation of qualitative change of integrins in response to eotaxin, because quantitative reduction of CD11a, CD11b and CD18 expression by troglitazone was not observed using flow cytometry. The PPARgamma agonist troglitazone has a potent inhibitory effect on eosinophil adhesion to ICAM-1, and this may be a therapeutic modality for the treatment of eosinophil-related diseases including bronchial asthma.
嗜酸性粒细胞在组织中的聚集和激活是过敏性炎症反应中的关键事件，而黏附分子在此过程中发挥着重要作用。我们之前证明，人类嗜酸性粒细胞表达一种核受体，即过氧化物酶体增殖物激活受体γ（PPARγ），并且用PPARγ激动剂刺激可减弱细胞因子/趋化因子诱导的嗜酸性粒细胞激活，如存活、趋化性和脱颗粒。在本研究中，我们研究了合成的PPARγ激动剂曲格列酮对细胞间黏附分子-1（ICAM-1）黏附的影响。从人类外周血中纯化嗜酸性粒细胞，并检测其对重组可溶性ICAM-1包被板的功能性黏附。我们发现，在存在嗜酸性粒细胞趋化因子的情况下，曲格列酮以浓度依赖的方式抑制嗜酸性粒细胞黏附。这种新活性似乎与整合素响应嗜酸性粒细胞趋化因子的定性变化调节有关，因为使用流式细胞术未观察到曲格列酮对CD11a、CD11b和CD18表达的定量减少。PPARγ激动剂曲格列酮对嗜酸性粒细胞与ICAM-1的黏附有强大的抑制作用，这可能是治疗包括支气管哮喘在内的嗜酸性粒细胞相关疾病的一种治疗方式。
