CD47, a ligand for the macrophage fusion receptor, participates in macrophage multinucleation
CD47, a ligand for the macrophage fusion receptor, participates in macrophage multinucleation
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DOI：
10.1074/jbc.m002334200
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发表时间：
2000-12-01
影响因子：
4.8
通讯作者：
Vignery, A
中科院分区：
文献类型：
--
作者：
Han, X;Sterling, H;Vignery, A
巨噬细胞融合受体（MFR），也称为P84/BIT/SIRP α/SHPS-1，是属于免疫球蛋白超家族的跨膜糖蛋白。以前，我们表明，MFR的表达是高度诱导的融合在巨噬细胞的发病，和MFR似乎发挥作用，巨噬细胞-巨噬细胞粘附/融合，导致多核。最近发现I4 P/CD 47作为MFR的配体，这使我们假设它在细胞-细胞融合开始时与CD 47相互作用。CD 47是一种跨膜糖蛋白，与MFR一样，属于免疫球蛋白超家族。我们发现，巨噬细胞表达造血形式的CD 47，其表达是诱导在融合的发病，但低于MFR的水平。一种谷胱甘肽S-转移酶CD 47融合蛋白，经工程改造含有CD 47的胞外结构域，结合巨噬细胞，与MFR缔合，并防止多核化。CD 47和MFR通过其氨基末端免疫球蛋白可变结构域结合。在针对CD 47的细胞外结构域产生的9种单克隆抗体中，3种阻断融合以及MFR-CD 47相互作用，而其它的没有作用。总之，这些数据表明，CD 47参与巨噬细胞多核化凭借与MFR在粘附/融合过程中的相互作用。
The macrophage fusion receptor (MFR), also called P84/BIT/SIRP alpha /SHPS-1, is a transmembrane glycoprotein that belongs to the superfamily of immunoglobulins. Previously, we showed that MFR expression is highly induced at the onset of fusion in macrophages, and that MFR appears to play a role in macrophage-macrophage adhesion/fusion leading to multinucleation. The recent finding that I4P/CD47 acts as a ligand for MFR led us to hypothesize that it interacts with CD47 at the onset of cell-cell fusion. CD47 is a transmembrane glycoprotein, which, like MFR, belongs to the superfamily of immunoglobulins. We show that macrophages express the hemopoietic form of CD47, the expression of which is induced at the onset of fusion, but to a lower level than MFR. A glutathione S-transferase CD47 fusion protein engineered to contain the extracellular domain of CD47, binds macrophages, associates with MFR, and prevents multinucleation. CD47 and MFR associate via their amino-terminal immunoglobulin variable domain. Of the nine monoclonal antibodies raised against the extracellular domain of CD47, three block fusion, as well as MFR-CD47 interaction, whereas the others have no effect. Together, these data suggest that CD47 is involved in macrophage multinucleation by virtue of interacting with MFR during adhesion/fusion.