The role of CS1 moiety of fibronectin in VLA4-mediated haemopoietic progenitor trafficking
The role of CS1 moiety of fibronectin in VLA4-mediated haemopoietic progenitor trafficking
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DOI：
10.1046/j.1365-2141.1997.d01-2120.x
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发表时间：
1997-04-01
影响因子：
6.5
通讯作者：
Papayannopoulou, T
中科院分区：
文献类型：
--
作者：
Craddock, CF;Nakamoto, B;Papayannopoulou, T
在体外，整合素VLA4通过与其配体VCAM-1和纤维连接蛋白CS1片段的相互作用介导造血祖细胞与骨髓基质的粘附。VLA4/VCAM-1途径与体内造血运输有关，因为针对VLA4和VCAM-1的抗体减少移植祖细胞的归巢（驻留）并动员祖细胞。然而，纤维连接蛋白CS1结构域在体内祖细胞转运中的作用尚未被探索，我们研究了竞争抑制VLA4/CS1通路对小鼠祖细胞归巢和动员的影响。用CS1抑制剂对骨髓细胞进行预孵育，在移植后3小时内不改变致死性照射小鼠骨髓中CFU-C或CFU-S12的数量。此外，持续给药CS1抑制剂不会增加外周血中CFU-C的数量。为了研究VLA4/CS1通路在更原始祖细胞运输中的作用，我们研究了CS1抑制剂是否能调动辐射保护细胞。与抗vcam -1的作用相反，它动员了能够拯救100%致命辐照小鼠的细胞，CS1抑制剂的施用并没有增加外周血中辐射保护细胞的数量。造血祖细胞也通过与VLA5的相互作用结合到纤维连接蛋白的RGD基序上，因此我们也研究了VLA5抗体对祖细胞归巢和动员的影响，VLA5抗体在3小时内没有改变骨髓沉积或增加循环造血祖细胞的数量。因此，这些研究表明，与VCAM-1相反，纤维连接蛋白的CS1部分在VLA4介导的体内祖细胞运输中不是一个重要的配体。
In vitro the integrin VLA4 mediates the adhesion of haemopoietic progenitors to bone marrow stroma through an interaction with its ligands VCAM-1 and the CS1 moiety of fibronectin. The VLA4/VCAM-1 pathway has been implicated in haemopoietic trafficking in vivo since antibodies to both VLA4 and VCAM-1 decrease the homing (lodgement) of transplanted progenitors and mobilize progenitors. However, the role of the CS1 domain of fibronectin in progenitor trafficking in vivo has not been explored, We studied the effect of competitive inhibition of the VLA4/CS1 pathway on progenitor homing and mobilization in mice. Pre-incubation of bone marrow cells with a CS1 inhibitor did not alter the number of CFU-C or CFU-S12 lodged to the bone marrow of lethally irradiated mice 3 h after transplantation. In addition, continuous administration of a CS1 inhibitor did not increase the number of CFU-C in the peripheral blood. In order to study the role of the VLA4/CS1 pathway in trafficking of more primitive progenitors we studied whether administration of a CS1 inhibitor mobilized radioprotective cells. In contrast to the effect of anti-VCAM-1 which mobilized cells capable of rescuing 100% of lethally irradiated mice, administration of a CS1 inhibitor did not increase the number of radioprotective cells in the peripheral blood. Haemopoietic progenitors also bind to the RGD motif of fibronectin through an interaction with VLA5 and we therefore also studied the effect of antibodies to VLA5 on progenitor homing and mobilization, Antibody to VLA5 did not alter bone marrow lodgement at 3 h or increase the number of circulating haemopoietic progenitors. These studies therefore imply that, in contrast to VCAM-1, the CS1 moiety of fibronectin is not a significant ligand in VLA4 mediated progenitor trafficking in vivo.