CCR2 regulates monocyte recruitment as well as CD4 T1 allorecognition after lung transplantation.
CCR2 regulates monocyte recruitment as well as CD4 T1 allorecognition after lung transplantation.
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DOI：
10.1111/j.1600-6143.2010.03101.x
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发表时间：
2010-05
期刊：
影响因子：
--
通讯作者：
Kreisel D
中科院分区：
文献类型：
--
作者：
Gelman AE;Okazaki M;Sugimoto S;Li W;Kornfeld CG;Lai J;Richardson SB;Kreisel FH;Huang HJ;Tietjens JR;Zinselmeyer BH;Patterson GA;Miller MJ;Krupnick AS;Kreisel D
移植物排斥反应仍然是肺移植后导致不良结局的一个棘手问题。阻断趋化因子通路在一些器官移植系统中已经产生了有希望的结果。先前的临床研究已经证实肺移植后CCR 2配体的上调。此外，在几种炎症模型中，CCR 2缺陷小鼠的肺损伤减弱。在这项研究中，我们研究了CCR 2在小鼠血管化原位肺移植模型中单核细胞募集和同种免疫反应中的作用。CCR 2配体MCP-1在肺移植后血清和同种异体移植物中上调。CCR 2对于单核细胞从骨髓动员到血流中以及对于肺同种异体移植物内CD 11 c+细胞的积累是至关重要的。移植物浸润受体CD 11 c+细胞的一部分表达受体和供体MHC分子。双光子成像表明受体CD 11 c+细胞与移植物内的受体T细胞相关。虽然受体CCR 2缺陷不能预防急性肺排斥反应，并与T细胞的移植物浸润增加有关，但它显著降低了CD 4 + Th 1的间接和直接同种异体识别。因此，CCR 2可能是一个潜在的靶点，以减轻肺移植后的同种免疫反应。
Graft rejection remains a formidable problem contributing to poor outcomes after lung transplantation. Blocking chemokine pathways have yielded promising results in some organ transplant systems. Previous clinical studies have demonstrated upregulation of CCR2 ligands following lung transplantation. Moreover, lung injury is attenuated in CCR2-deficient mice in several inflammatory models. In this study, we examined the role of CCR2 in monocyte recruitment and alloimmune responses in a mouse model of vascularized orthotopic lung transplantation. The CCR2 ligand MCP-1 is upregulated in serum and allografts following lung transplantation. CCR2 is critical for the mobilization of monocytes from the bone marrow into the bloodstream and for the accumulation of CD11c+ cells within lung allografts. A portion of graft-infiltrating recipient CD11c+ cells expresses both recipient and donor MHC molecules. Two-photon imaging demonstrates that recipient CD11c+ cells are associated with recipient T cells within the graft. While recipient CCR2 deficiency does not prevent acute lung rejection and is associated with increased graft infiltration by T cells, it significantly reduces CD4+ Th1 indirect and direct allorecognition. Thus, CCR2 may be a potential target to attenuate alloimmune responses after lung transplantation.
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影响因子：
14.8
作者：
Krupnick, Alexander S.;Lin, Xue;Li, Wenjun;Okazaki, Mikio;Lai, Jiaming;Sugimoto, Seiichiro;Richardson, Steven B.;Kornfeld, Christopher G.;Garbow, Joel R.;Patterson, G. Alexander;Gelman, Andrew E.;Kreisel, Daniel
通讯作者：
Kreisel, Daniel
影响因子：
6.2
作者：
Bharat, Ankit;Narayanan, Kishore;Mohanakumar, Thalachallour
通讯作者：
Mohanakumar, Thalachallour
影响因子：
4.4
作者：
Gelman, Andrew E.;Okazaki, Mikio;Kreisel, Daniel
通讯作者：
Kreisel, Daniel
影响因子：
6
作者：
Chiu, BC;Freeman, CM;Chensue, SW
通讯作者：
Chensue, SW
DOI：
10.1084/jem.192.10.1515
发表时间：
2000-11-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hancock WW;Lu B;Gao W;Csizmadia V;Faia K;King JA;Smiley ST;Ling M;Gerard NP;Gerard C
通讯作者：
Gerard C