Endothelial selectins and vascular cell adhesion molecule-1 promote hematopoietic progenitor homing to bone marrow
Endothelial selectins and vascular cell adhesion molecule-1 promote hematopoietic progenitor homing to bone marrow
复制标题
DOI：
10.1073/pnas.95.24.14423
复制
发表时间：
1998-11-24
影响因子：
11.1
通讯作者：
Wagner, DD
中科院分区：
文献类型：
--
作者：
Frenette, PS;Subbarao, S;Wagner, DD
骨髓移植后造血祖细胞（HPC）归巢到骨髓（BM）的粘附机制知之甚少。我们研究了内皮选择素和血管细胞粘附分子-1（VCAM-1）在这一过程中的作用。与野生型受体相比，P-和E-选择素（P/E-/-）缺陷的致死性辐照受体小鼠，用最小数量（小于或等于5 × 10（4））的野生型BM细胞重建，在手术中存活率很低。P/E-/-小鼠在致死剂量照射后的过量死亡率可能是由HPC归巢缺陷引起的。事实上，我们观察到，在P/E-/-动物（脾切除或脾完整）中，HPC向BM的募集减少。当给予功能阻断VCAM-1抗体时，P/E-/-受体小鼠的BM归巢进一步受损。与仅用IgG处理的P/E-/-小鼠或用抗VCAM-1或IgG处理的野生型小鼠相比，用抗VCAM-1处理的P/E-/-小鼠移植后14小时的循环HPC显著增加。我们的结果表明，内皮选择素在HPC归巢BM中起重要作用，致死剂量照射后HPC的最佳募集需要选择素和BM内皮上表达的VCAM-1的共同作用。
The adhesive mechanisms allowing hemato poietic progenitor cells (HPC) homing to the bone marrow (BM) after BM transplantation are poorly understood. We investigated the role of endothelial selectins and vascular cell adhesion molecule-1 (VCAM-1) in this process. Lethally irradiated recipient mice deficient in both P-and E-selectins (P/E-/-), reconstituted with minimal numbers (less than or equal to 5 x 10(4)) of wild-type BM cells, poorly survived the procedure compared with wild-type recipients. Excess mortality in P/E-/- mice, after a lethal dose of irradiation, was likely caused by a defect of HPC homing. Indeed, we observed that the recruitment of HPC to the BM was reduced in P/E-/- animals, either splenectomized or spleen-intact. Homing into the BM of P/E-/- recipient mice was further compromised when a function-blocking VCAM-1 antibody was administered. Circulating HPC, 14 hr after transplantation, were greatly in creased in P/E-/- mice treated with anti-VCAM-1 compared with P/E-/- mice treated with just IgG or wild-type mice treated with either anti-VCAM-1 or IgG. Our results indicate that endothelial selectins play an important role in HPC homing to the BM, Optimal recruitment of HPC after lethal doses of irradiation requires the combined action of both selectins and VCAM-1 expressed on endothelium of the BM.