Shear Stress-Dependent Downregulation of the Adhesion-G Protein-Coupled Receptor CD97 on Circulating Leukocytes upon Contact with Its Ligand CD55
Shear Stress-Dependent Downregulation of the Adhesion-G Protein-Coupled Receptor CD97 on Circulating Leukocytes upon Contact with Its Ligand CD55
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DOI：
10.4049/jimmunol.1202192
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发表时间：
2013-04-01
影响因子：
4.4
通讯作者：
Hamann, Jorg
中科院分区：
文献类型：
--
作者：
Karpus, Olga N.;Veninga, Henrike;Hamann, Jorg
粘附G蛋白偶联受体（aGPCR）是两个亚基分子，由粘附性细胞外a亚基与七跨膜B亚基非共价偶联组成。两个亚基之间的合作和内源性配体对aGPCR功能的影响知之甚少。在这项研究中，我们研究了泛白细胞aGPCR CD 97及其配体CD 55之间的相互作用。我们发现，CD 55缺陷小鼠的白细胞表达的细胞表面CD 97的水平显着增加后，正常化转移到野生型小鼠，因为与白细胞和基质细胞上的CD 55的接触。两种CD 97亚基的下调发生在体内首次接触CD 55后数分钟内，这与可溶性CD 97血浆水平的增加相关。在体外，下调CD 55缺陷的白细胞与野生型血细胞共培养的CD 97是严格依赖于剪切力。在体内，CD 55介导的CD 97下调需要完整的循环，并且在缺乏与血流接触的细胞（如小胶质细胞）上未观察到。值得注意的是，CD 97的从头连接不激活癌细胞中由CD 97组成性接合的信号分子，如ERK和蛋白激酶B/Akt。我们的结论是，CD 55下调CD 97表面表达循环白细胞的过程中，需要物理力量，但根据目前的证据并不诱导受体信号。这种调节可以限制CD 97-CD 55介导的细胞粘附到组织部位。免疫学杂志，2013，190：3740-3748。
Adhesion G protein-coupled receptors (aGPCRs) are two-subunit molecules, consisting of an adhesive extracellular a subunit that couples noncovalently to a seven-transmembrane b subunit. The cooperation between the two subunits and the effect of endogenous ligands on the functioning of aGPCRs is poorly understood. In this study, we investigated the interaction between the pan-leukocyte aGPCR CD97 and its ligand CD55. We found that leukocytes from CD55-deficient mice express significantly increased levels of cell surface CD97 that normalized after transfer into wild-type mice because of contact with CD55 on both leukocytes and stromal cells. Downregulation of both CD97 subunits occurred within minutes after first contact with CD55 in vivo, which correlated with an increase in plasma levels of soluble CD97. In vitro, downregulation of CD97 on CD55-deficient leukocytes cocultured with wild-type blood cells was strictly dependent on shear stress. In vivo, CD55-mediated downregulation of CD97 required an intact circulation and was not observed on cells that lack contact with the blood stream, such as microglia. Notably, de novo ligation of CD97 did not activate signaling molecules constitutively engaged by CD97 in cancer cells, such as ERK and protein kinase B/Akt. We conclude that CD55 downregulates CD97 surface expression on circulating leukocytes by a process that requires physical forces, but based on current evidence does not induce receptor signaling. This regulation can restrict CD97-CD55-mediated cell adhesion to tissue sites. The Journal of Immunology, 2013, 190: 3740-3748.