PERIPHERALIZATION OF HEMATOPOIETIC PROGENITORS IN PRIMATES TREATED WITH ANTI-VLA4 INTEGRIN
PERIPHERALIZATION OF HEMATOPOIETIC PROGENITORS IN PRIMATES TREATED WITH ANTI-VLA4 INTEGRIN
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DOI：
10.1073/pnas.90.20.9374
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发表时间：
1993-10-15
影响因子：
11.1
通讯作者：
NAKAMOTO, B
中科院分区：
文献类型：
--
作者：
PAPAYANNOPOULOU, T;NAKAMOTO, B
造血细胞与骨髓基质成分的相互作用是维持正常造血所必需的，骨髓基质是造血细胞在成年个体中“归巢”的独特场所。然而，负责归巢和造血细胞与骨髓基质细胞在体内持续相互作用的特定分子，或参与祖细胞/干细胞通过血流运输的那些分子尚未确定。粘附受体，特别是整合素家族的一个大的剧目，似乎在促进造血干细胞体外培养的骨髓基质细胞的粘附中发挥了突出的作用。为了测试细胞粘附分子在体内的功能作用，我们用抗α 4-或抗β 2-整联蛋白抗体全身治疗灵长类动物，其抗原存在于大多数造血祖细胞和许多分化细胞中。我们发现，抗α 4（抗VLA 4，抗CD 49 d），而不是抗β 2（抗CD 18）治疗选择性动员祖细胞进入血流（高达200倍）。外周化涉及红系、髓系和混合祖细胞;在单次抗VLA 4注射后24小时可检测到;并持续超过治疗天数。抗VLA 4治疗加性增强了具有粒细胞集落刺激因子前期的动物中祖细胞的外周化。这些数据提供了关于VLA 4抗原参与体内祖细胞运输的见解，并且与用于移植的外周血干细胞的收集相关。
Interaction of hemopoietic cells with the elements of the underlying bone marrow stroma, the unique site of their ''homing'' in adult individuals, is essential for sustained normal hemopoiesis. However, the specific molecules responsible for homing and for the continuing interaction of hemopoietic cells with the bone marrow stromal cells in vivo, or those involved in progenitor/stem cell trafficking through the bloodstream, have not been defined. A large repertoire of adhesion receptors, especially of the integrin family, appear to play a prominent role in promoting adhesion of hemopoietic stem cells to cultured marrow stromal cells in vitro. To test the functional role of cytoadhesion molecules in vivo, we treated primates systemically with either anti-alpha4- or anti-beta2-integrin antibodies, whose antigens are found in the majority of hemopoietic progenitors and in many differentiated cells. We found that anti-alpha4 (anti-VLA4, anti-CD49d) but not anti-beta2 (anti-CD18) treatment selectively mobilized progenitors into the bloodstream (up to 200-fold). Peripheralization involved erythroid, myeloid, and mixed progenitors; was detectable 24 hr after a single anti-VLA4 injection; and lasted beyond the days of treatment. Anti-VLA4 treatment additively augmented peripheralization of progenitors in animals with a preceding course of granulocyte-colony-stimulating factor. These data provide insight on the involvement of VLA4 antigens in the in vivo trafficking of progenitors and are of relevance to collection of peripheral blood stem cells for transplantation.