EOTAXIN - A POTENT EOSINOPHIL CHEMOATTRACTANT CYTOKINE DETECTED IN A GUINEA-PIG MODEL OF ALLERGIC AIRWAYS INFLAMMATION
EOTAXIN - A POTENT EOSINOPHIL CHEMOATTRACTANT CYTOKINE DETECTED IN A GUINEA-PIG MODEL OF ALLERGIC AIRWAYS INFLAMMATION
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DOI：
10.1084/jem.179.3.881
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发表时间：
1994-03-01
影响因子：
15.3
通讯作者：
WILLIAMS, TJ
中科院分区：
文献类型：
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作者：
JOSE, PJ;GRIFFITHSJOHNSON, DA;WILLIAMS, TJ
嗜酸性粒细胞聚集是变应性炎症反应的一个显著特征，例如发生在变应性哮喘患者的肺中的那些，但涉及的内源性化学引诱物尚未被鉴定。我们已经在一个建立的过敏性炎症模型中研究了这一点，使用体内系统来产生和测定相关活性。用卵清蛋白雾化吸入致敏豚鼠后，间隔一段时间取支气管肺泡灌洗液（BAL）。在未致敏试验豚鼠中皮内注射BAL液，并测量静脉注射In-111-嗜酸性粒细胞的蓄积。过敏原激发后30 min检测到活性，3 ~ 6 h达到峰值，24 h降至低水平。使用高效液相色谱技术结合皮肤试验纯化3小时BAL液。微测序揭示了来自趋化细胞因子的血小板因子4超家族的C-C分支的新蛋白。该蛋白质“eotaxin "与人MCP-1具有53%的同源性，与豚鼠MCP-1 α具有44%的同源性，与人MCP-1 α具有31%的同源性，与人RANTES具有26%的同源性。激光解吸飞行时间质谱分析给出了四个不同的信号（8.15，8.38，8.81和9.03 kD），可能反映了差异O-糖基化。嗜酸性粒细胞趋化因子是高度有效的，在皮肤中以1-2 pmol剂量诱导大量In-111-嗜酸性粒细胞蓄积，但不诱导显著的In-111-嗜中性粒细胞蓄积。嗜酸性粒细胞趋化因子在体外是豚鼠和人嗜酸性粒细胞的有效刺激物。人重组RANTES、MIP-1 α和MCP-1在诱导豚鼠皮肤中In-111-嗜酸性粒细胞蓄积方面均无活性;然而，有证据表明嗜酸性粒细胞活化趋化因子与豚鼠嗜酸性粒细胞上的RANTES共享一个结合位点。这是第一次描述一种有效的嗜酸性粒细胞趋化细胞因子在体内产生，并建议类似的分子可能是重要的，在人类哮喘肺的可能性。
Eosinophil accumulation is a prominent feature of allergic inflammatory reactions, such as those occurring in the lung of the allergic asthmatic, but the endogenous chemoattractants involved have not been identified. We have investigated this in an established model of allergic inflammation, using in vivo systems both to generate and assay relevant activity. Bronchoalveolar lavage (BAL) fluid was taken from sensitized guinea pigs at intervals after aerosol challenge with ovalbumin. BAL fluid was injected intradermally in unsensitized assay guinea pigs and the accumulation of intravenously injected In-111-eosinophils was measured. Activity was detected at 30 min after allergen challenge, peaking from 3 to 6 h and declining to low levels by 24 h. 3-h BAL fluid was purified using high performance liquid chromatography techniques in conjunction with the skin assay. Microsequencing revealed a novel protein from the C-C branch of the platelet factor 4 superfamily of chemotactic cytokines. The protein, ''eotaxin'' exhibits homology of 53% with human MCP-1, 44% with guinea pig MCP-1 alpha 31% with human MCP-1 alpha, and 26% with human RANTES. Laser desorption time of flight mass analysis gave four different signals (8.15, 8.38, 8.81, and 9.03 kD), probably reflecting differential O-glycosylation. Eotaxin was highly potent, inducing substantial In-111-eosinophil accumulation at a 1-2-pmol dose in the skin, but did not induce significant In-111-neutrophil accumulation. Eotaxin was a potent stimulator of both guinea pig and human eosinophils in vitro. Human recombinant RANTES, MIP-1 alpha, and MCP-1 were all inactive in inducing In-111-eosinophil accumulation in guinea pig skin; however, evidence was obtained that eotaxin shares a binding site with RANTES on guinea pig eosinophils. This is the first description of a potent eosinophil chemoattractant cytokine generated in vivo and suggests the possibility that similar molecules may be important in the human asthmatic lung.