Variations in Eosinophil Chemokine Responses: An Investigation of CCR1 and CCR3 Function, Expression in Atopy, and Identification of a Functional CCR1 Promoter1
Variations in Eosinophil Chemokine Responses: An Investigation of CCR1 and CCR3 Function, Expression in Atopy, and Identification of a Functional CCR1 Promoter1
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嗜酸性粒细胞趋化因子反应的变化：CCR1 和 CCR3 功能的研究、特应性的表达以及功能性 CCR1 启动子的鉴定1
作者：
R. Phillips;Victoria E. L. Stubbs;M. Henson;T. Williams;J. Pease;I. Sabroe
我们之前在一小组供体中发现，来自一亚组个体的嗜酸性粒细胞对CC趋化因子配体（CCL）11/eotaxin和CCL3/巨噬-炎症蛋白-1α在嗜酸性粒细胞形状变化（CCL3/巨噬-炎症蛋白-1α-高反应（MHR）供体）的检测中具有相同的反应。在这项研究中，我们研究了CCL3在73名供者嗜酸性粒细胞反应中的功能作用。通过其嗜酸性粒细胞形状变化反应确定的MHR供体占供体池的19%。来自这些供体的嗜酸性粒细胞CCR1表达增加，也经历了ccl3介导的趋化和CD11b上调。所有MHR献血者均有特异反应相关疾病史。在进一步的研究中，我们前瞻性地招募了110名受试者，将其细分为非特应性或特应性，并研究了CCR1和CCR3在嗜酸性粒细胞、嗜碱性粒细胞、单核细胞和中性粒细胞中的表达。嗜酸性粒细胞CCR1表达在特应性中呈非正态分布，尽管较高的CCR1表达水平并不能预测特应性或特应性疾病的诊断。我们鉴定了CCR1启动子并研究了其功能。我们在转录起始位点的177bp内发现了一个最小启动子，并在白细胞细胞系中发现了一个促进表达的上游增强子区域。总的来说，这些数据表明，MHR个体形成了一个重要的亚群，当与过敏性疾病的诊断相关时，可能需要定制治疗来调节嗜酸性粒细胞的募集。鉴定功能性CCR1启动子将有助于研究这种潜在重要临床表型的可能遗传决定因素。
We previously showed in a small group of donors that eosinophils from a subgroup of individuals responded equipotently to CC chemokine ligand (CCL)11/eotaxin and CCL3/macrophage-inflammatory protein-1α in assays of eosinophil shape change (CCL3/macrophage-inflammatory protein-1α-highly responsive (MHR) donors). In this study, we investigated the functional role of CCL3 in eosinophil responses in 73 donors. MHR donors, identified by their eosinophil shape change responses, represented ∼19% of the donor pool. Eosinophils from these donors showed increased eosinophil CCR1 expression and also underwent CCL3-mediated chemotaxis and up-regulation of CD11b. All MHR donors gave a history of atopy-associated diseases. In a further study, we prospectively recruited 110 subjects, subdivided into nonatopics or atopics, and investigated expression of CCR1 and CCR3 on eosinophils, basophils, monocytes, and neutrophils. Eosinophil CCR1 expression was non-normally distributed in atopics, although higher CCR1 expression levels were not predictive of a diagnosis of atopy or atopic disease. We identified the CCR1 promoter and investigated its function. We found a minimal promoter within 177 bp of the transcription start site, and an upstream enhancer region that facilitated expression in leukocyte cell lines. Collectively, these data demonstrate that MHR individuals form an important subgroup that, when associated with a diagnosis of allergic disease, may require tailored therapy to modulate eosinophil recruitment. Identification of a functional CCR1 promoter will facilitate the study of possible genetic determinants underlying this potentially important clinical phenotype.
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DOI：
10.1164/ajrccm.153.4.8616572
发表时间：
1996-04-01
影响因子：
24.7
作者：
Alam, R;York, J;Ida, N
通讯作者：
Ida, N
巨噬细胞炎症蛋白 1 α 影响抗原特异性气道炎症中嗜酸性粒细胞的募集。
DOI：
10.1002/eji.1830250140
发表时间：
1995
期刊：
European journal of immunology.
影响因子：
--
作者：
Lukacs,NW;Strieter,RM;Shaklee,CL;Chensue,SW;Kunkel,SL
通讯作者：
Kunkel,SL
人类趋化因子受体 CCR3 的转录调控：果蝇和人类之间保守的罕见 TATA-less 启动子结构的证据。
影响因子：
4.4
作者：
Vijh,Sujata;Dayhoff,DeboraE;Wang,CarolE;Imam,Zakaria;Ehrenberg,PhilipK;Michael,NelsonL
通讯作者：
Michael,NelsonL
细胞因子诱导的嗜酸性粒细胞跨内皮迁移。
DOI：
--
发表时间：
1994
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Ebisawa,M;Yamada,T;Bickel,C;Klunk,D;Schleimer,RP
通讯作者：
Schleimer,RP
影响因子：
15.9
作者：
Ponath, PD;Qin, SX;Mackay, CR
通讯作者：
Mackay, CR