Selective binding and presentation of CCL5 by discrete tissue microenvironments during renal inflammation.

Selective binding and presentation of CCL5 by discrete tissue microenvironments during renal inflammation.
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肾脏炎症期间离散组织微环境选择性结合和呈递 CCL5。

DOI:
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发表时间:
2007
影响因子:
13.6
通讯作者:
P. Nelson
P. Nelson
中科院分区:
医学1区
文献类型:
--
作者:
S. Segerer;R. Djafarzadeh;H. Gröne;C. Weingart;D. Kerjaschki;C. Weber;A. Kungl;H. Regele;A. Proudfoot;P. Nelson

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在肾脏炎症过程中,T细胞被差异性地募集到肾小管上皮细胞。表面结构对趋化因子的选择性呈递可能是这种现象的部分原因。为了更好地表征组织环境对趋化因子的呈递,选择了具有明确结构的示例性趋化因子,并开发了固定存档组织切片上蛋白质的结合测定。这篇文章描述了趋化因子CCL5与肾脏结构的选择性结合。在保存良好的肾脏中,CCL5显示与内皮区域、间质细胞外基质、肾小管上皮细胞和肾小管基底膜结合,但很少与肾小球结构结合。相反,在急性同种异体移植肾小球炎(其中T细胞在肾小球中积聚)的肾活检中观察到CCL5与肾小球组分的结合。N末端介导受体结合,而两簇碱性氨基酸残基((44)RKNR(47)和(55)KKWVR(59))参与细胞外结构对CCL 5的呈递。任一环的突变废除了CCL5与组织切片的结合。N末端的变化和防止更高阶寡聚化的突变没有改变结合模式。这些数据表明,肾间室不同的能力,目前趋化因子,这可能有助于解释白细胞的差异招聘在同种异体移植物损伤。CCL5中的两个碱性残基簇对于CCL5与组织切片的充分结合是必需的。
T cells are differentially recruited to the tubulointerstitium during renal inflammation. The selective presentation of chemokines by surface structures may in part underlie this phenomenon. In an attempt to better characterize the presentation of chemokines by tissue environments an exemplary chemokine with a well-defined structure was selected, and a binding assay for the protein on fixed archival tissue sections was developed. This article describes the selective binding of the chemokine CCL5 to renal structures. CCL5 was shown to bind to endothelial regions, interstitial extracellular matrix, tubular epithelial cells, and tubular basement membranes but rarely to glomerular structures in well-preserved kidneys. In contrast, binding of CCL5 to glomerular components was seen in renal biopsies with acute allograft glomerulitis (in which T cells accumulate in glomeruli). The N terminus mediates receptor binding, whereas two clusters of basic amino acid residues ((44)RKNR(47) and (55)KKWVR(59)) are involved in the presentation of CCL5 by extracellular structures. Mutation of either loop abrogated CCL5 binding to tissue sections. Variations of the N terminus and a mutation that prevents higher order oligomerization did not change the binding pattern. The data suggest that renal compartments differ in their capacity to present chemokines, which may help explain the differential recruitment of leukocytes during allograft injury. Both clusters of basic residues in CCL5 are necessary for sufficient binding of CCL5 to tissue sections.
DOI: --
发表时间: 2000-03
影响因子: 21.1
作者:
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通讯作者: P. Murphy;M. Baggiolini;I. Charo;C. Hébert;R. Horuk;K. Matsushima;L. Miller;J. Oppenheim;C. Power-C.
从猪血小板中纯化两种肝素结合蛋白及其与人分泌的血小板蛋白的同源性。
DOI: --
发表时间: 1983
期刊: Blood
影响因子: 20.3
作者:
Rucinski,B;Poggi,A;James,P;Holt,JC;Niewiarowski,S
通讯作者: Niewiarowski,S
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发表时间: 1985-07
影响因子: 3.9
作者:
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