Chihara J
Department of Clinical and Laboratory Medicine, Akita University School of Medicine, Japan.
Nihon Kyobu Shikkan Gakkai Zasshi. 1996 Dec;34 Suppl:116-20.
Patients with hypereosinophila have at least two subpopulation of eosinophils: "normodense" and "hypodense". Hypodense eosinophils can be distinguished by their increased expression of various membrane receptors including IL-5 receptors (J Exp Med 172: 1347) and by the expression of particular proteins (J Immunol 142: 4416). Recently, adhesion molecules have also been found to play an important role in the inflammatory processes in allergic disease. 1) Adhesion molecules were found to be strongly expressed on eosinophils from patients with asthma. 2) Platelet activating factor and induced the expression of adhesion molecules as did the supernatant of mononuclear cells from mite-allergic patients with asthma stimulated either with mite allergen or with a combination of recombinant IL-3, GM-CSF, and IL-5 (Immunol, Lett. 42: 25, '94, & 46: 241, '95). 3) Patients with bronchial asthma had a high level of soluble ICAM-1) (Lancet. 343: 1108, '94). Moreover, the presence of a large variety of membrane receptors and the identification of cytotoxic molecules (mainly granule basic proteins) indicate that eosinophils should be considered effector cells. Therefore the release of granule proteins in response to ICAM-1 and its ligands was studied. The concentrations of eosinophil cationic protein and eosinophil-derived neurotoxin in supernatants of eosinophils were significantly greater in the presence of recombinant soluble ICAM-1 than in its absence (p < 0.05). These results suggest that signals from ICAM-1 and its ligands induce eosinophil activation and are involved in degranulation of eosinophil granule proteins. In addition, reactive oxygen species generated by eosinophils have also been considered capable of causing airway injury at sites of inflammation. The effect of recombinant soluble ICAM-1 and its ligands on eosinophil-induced radical oxygen products was studied. Recombinant soluble ICAM-1 augmented eosinophil oxidative metabolism. Therefore, signaling via adhesion molecules might play an important role in the pathogenesis of allergic inflammation. Specifically, it may activate eosinophils and increase oxidative metabolism or cause degranulation of eosinophil granule proteins.
“正常密度”和“低密度”。低密度嗜酸性粒细胞可通过其多种膜受体(包括IL-5受体,《实验医学杂志》172:1347)表达增加以及特定蛋白质的表达(《免疫学杂志》142:4416)来区分。最近,黏附分子也被发现在过敏性疾病的炎症过程中起重要作用。1)发现黏附分子在哮喘患者的嗜酸性粒细胞上强烈表达。2)血小板活化因子以及经螨过敏原或重组IL-3、GM-CSF和IL-5联合刺激的哮喘螨过敏患者的单核细胞上清液均可诱导黏附分子的表达(《免疫学快报》42:25,1994年,及46:241,1995年)。3)支气管哮喘患者的可溶性ICAM-1水平较高(《柳叶刀》343:1108,1994年)。此外,多种膜受体的存在以及细胞毒性分子(主要是颗粒碱性蛋白)的鉴定表明嗜酸性粒细胞应被视为效应细胞。因此,研究了嗜酸性粒细胞对ICAM-1及其配体的反应中颗粒蛋白的释放。在存在重组可溶性ICAM-1的情况下,嗜酸性粒细胞上清液中嗜酸性粒细胞阳离子蛋白和嗜酸性粒细胞衍生神经毒素的浓度显著高于不存在时(p<0.05)。这些结果表明,来自ICAM-1及其配体的信号诱导嗜酸性粒细胞活化,并参与嗜酸性粒细胞颗粒蛋白的脱颗粒。此外,嗜酸性粒细胞产生的活性氧也被认为能够在炎症部位引起气道损伤。研究了重组可溶性ICAM-1及其配体对嗜酸性粒细胞诱导的活性氧产物的影响。重组可溶性ICAM-1增强了嗜酸性粒细胞的氧化代谢。因此,通过黏附分子的信号传导可能在过敏性炎症的发病机制中起重要作用。具体而言,它可能激活嗜酸性粒细胞并增加氧化代谢或导致嗜酸性粒细胞颗粒蛋白的脱颗粒。