Molecular pathways in bone marrow homing:: dominant role of α4β1 over β2-integrins and selectins
Molecular pathways in bone marrow homing:: dominant role of α4β1 over β2-integrins and selectins
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DOI：
10.1182/blood.v98.8.2403
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发表时间：
2001-10-15
期刊：
影响因子：
20.3
通讯作者：
Scott, LM
中科院分区：
文献类型：
--
作者：
Papayannopoulou, T;Priestley, GV;Scott, LM
静脉内施用的造血细胞在骨髓内的特异性保留是复杂的多步骤过程。尽管最近的见解，分子力学管理这一过程仍然在很大程度上不确定。本研究探讨了β 2-整合素对骨髓祖细胞归巢和再增殖动力学的影响。使用抗功能抗体和遗传缺陷细胞。此外，在归巢实验中，三重选择素缺陷小鼠被用作缺陷（选择素或β（2））或正常细胞的受体。无论是β（2）无效或选择素无效细胞进入正常或选择素缺陷受体的归巢模式与正常细胞给予正常受体的归巢模式相似。此外，脾集落形成单位和移植后2周的早期骨髓重建活性与对照细胞无显著差异。这些数据与β（2）-整联蛋白和选择素在成熟白细胞的粘附/迁移级联中的重要性相反。这种差异可能与骨髓特殊的血流动力学有关。虽然移植后早期死亡可以在CD 18和选择素缺乏的受体中看到，但这些死亡归因于脓毒性并发症而不是归巢缺陷。然而，当β 2或选择素缺失的供体细胞在移植到正常或选择素缺陷的受体之前用抗α 4抗体处理时，发现归巢的显著抑制（>90%）。数据表明，单独的α 4 β 1/血管细胞粘附分子1通路能够提供骨髓内细胞的有效捕获，但如果其功能受损，则其它途径，即β（2）-整联蛋白或选择素的协同作用就暴露出来。(C)2001年，美国血液学会。
The specific retention of intravenously administered hemopoietic cells within bone marrow is a complex multistep process. Despite recent insights, the molecular mechanics governing this process remain largely undefined. This study explored the influence of beta (2)-integrins on the homing to bone marrow and repopulation kinetics of progenitor cells. Both antifunctional antibodies and genetically deficient cells were used. In addition, triple selectin-deficient mice were used as recipients of either deficient (selectin or beta (2)) or normal cells in homing experiments. The homing patterns of either beta (2) null or selectin null cells into normal or selectin-deficient recipients were similar to those of normal cells given to normal recipients. Furthermore, spleen colony-forming units and the early bone marrow repopulating activity for the first 2 weeks after transplantation were not significantly different from those of control cells. These data are in contrast to the importance of beta (2)-integrin and selectins in the adhesion/migration cascade of mature leukocytes. The special bone marrow flow hemodynamics may account for these differences. Although early deaths after transplantation can be seen in recipients deficient in CD18 and selectin, these are attributed to septic complications rather than homing defects. However, when beta (2)- or selectin-null donor cells are treated with anti-alpha (4) antibodies before their transplantation to normal or selectin-deficient recipients, a dramatic inhibition of homing (>90%) was found. The data suggest that the alpha (4)beta (1)/vascular cell adhesion molecule-1 pathway alone is capable of providing effective capture of cells within the bone marrow, but if its function is compromised, the synergistic contribution of other pathways, that is, beta (2)-integrins or selectins, is uncovered. (C) 2001 by The American Society of Hematology.