Papayannopoulou T, Nakamoto B
Department of Medicine, University of Washington, Seattle 98195.
Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9374-8. doi: 10.1073/pnas.90.20.9374.
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-alpha 4- or anti-beta 2-integrin antibodies, whose antigens are found in the majority of hemopoietic progenitors and in many differentiated cells. We found that anti-alpha 4 (anti-VLA4, anti-CD49d) but not anti-beta 2 (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.
造血细胞与潜在骨髓基质成分（成体个体中造血细胞“归巢”的独特部位）之间的相互作用对于维持正常造血至关重要。然而，负责归巢以及造血细胞在体内与骨髓基质细胞持续相互作用的特定分子，或者参与祖细胞/干细胞通过血流迁移的分子，尚未明确。大量的黏附受体，尤其是整合素家族的受体，似乎在促进造血干细胞与体外培养的骨髓基质细胞黏附中发挥着重要作用。为了测试细胞黏附分子在体内的功能作用，我们用抗α4或抗β2整合素抗体对灵长类动物进行全身治疗，这些抗体的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α4（抗VLA4、抗CD49d）而非抗β2（抗CD18）治疗可选择性地将祖细胞动员到血流中（高达200倍）。外周化涉及红系、髓系和混合祖细胞；单次注射抗VLA4后24小时即可检测到；并且持续到治疗结束后的数天。抗VLA4治疗可累加增强先前接受粒细胞集落刺激因子治疗的动物中祖细胞的外周化。这些数据为VLA4抗原参与祖细胞的体内迁移提供了见解，并且与用于移植的外周血干细胞采集相关。
