Muro Shigeo, Hamid Qutayba, Olivenstein Ronald, Taha Rame, Rokach Joshua, Powell William S
Department of Medicine, McGill University, Montreal, Quebec, Canada.
J Allergy Clin Immunol. 2003 Oct;112(4):768-74. doi: 10.1016/s0091-6749(03)01888-8.
5-Oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) is an arachidonic acid metabolite with potent in vitro chemoattractant effects on eosinophils and neutrophils. It has also been shown to induce pulmonary eosinophilia in Brown Norway rats, but it is not known whether it is active in human beings in vivo.
To determine whether 5-oxo-ETE can induce cellular infiltration in patients with atopic asthma and nonatopic control subjects after intradermal administration.
5-Oxo-ETE was administered intradermally to 11 patients with atopic asthma and 10 nonatopic control subjects. Skin biopsy specimens were taken 6 or 24 hours later and examined by immunocytochemistry for cells expressing specific markers for eosinophils (major basic protein), neutrophils (elastase), macrophages (CD68), lymphocytes (CD3), and mast cells (tryptase).
5-Oxo-ETE (1.5 and 5 microg) elicited the infiltration of both eosinophils and neutrophils into the skin in both control and atopic asthmatic subjects. Increased numbers of eosinophils were observed at 6 and 24 hours after injection, whereas significantly elevated neutrophil numbers were present only after 24 hours. Eosinophils were >3 times higher in patients with atopic asthma compared with control subjects after injection of the highest dose of 5-oxo-ETE. Macrophage numbers were also elevated, but only at the highest dose of 5-oxo-ETE. No effects were observed on the numbers of either lymphocytes or mast cells.
5-Oxo-ETE elicits the infiltration of eosinophils and neutrophils into the skin of human beings in vivo after intradermal administration. Asthmatic subjects are more responsive to this substance than nonallergic control subjects. These results suggest that 5-oxo-ETE may be an important mediator of inflammation.
5-氧代-6,8,11,14-二十碳四烯酸（5-氧代-ETE）是一种花生四烯酸代谢产物，对嗜酸性粒细胞和中性粒细胞具有强大的体外趋化作用。研究还表明，它可诱导棕色挪威大鼠发生肺部嗜酸性粒细胞增多，但尚不清楚其在人体体内是否具有活性。
确定皮内注射5-氧代-ETE后，其能否在特应性哮喘患者和非特应性对照受试者中诱导细胞浸润。
对11例特应性哮喘患者和10例非特应性对照受试者进行皮内注射5-氧代-ETE。6或24小时后取皮肤活检标本，通过免疫细胞化学检测表达嗜酸性粒细胞（主要碱性蛋白）、中性粒细胞（弹性蛋白酶）、巨噬细胞（CD68）、淋巴细胞（CD3）和肥大细胞（组织蛋白酶）特异性标志物的细胞。
在对照受试者和特应性哮喘受试者中，5-氧代-ETE（1.5和5微克）均引起嗜酸性粒细胞和中性粒细胞浸润至皮肤。注射后6小时和24小时观察到嗜酸性粒细胞数量增加，而中性粒细胞数量仅在24小时后显著升高。注射最高剂量的5-氧代-ETE后，特应性哮喘患者的嗜酸性粒细胞数量比对照受试者高3倍以上。巨噬细胞数量也有所增加，但仅在最高剂量的5-氧代-ETE时出现。未观察到对淋巴细胞或肥大细胞数量的影响。
皮内注射5-氧代-ETE后，其在人体体内可引起嗜酸性粒细胞和中性粒细胞浸润至皮肤。哮喘受试者对该物质的反应比非过敏对照受试者更敏感。这些结果表明，5-氧代-ETE可能是一种重要的炎症介质。
