Miyake K, Underhill C B, Lesley J, Kincade P W
Immunobiology & Cancer Program, Oklahoma Medical Research Foundation, Oklahoma City 73104.
J Exp Med. 1990 Jul 1;172(1):69-75. doi: 10.1084/jem.172.1.69.
A cell adhesion model was previously used to select a series of monoclonal antibodies (mAbs), which were subsequently found to recognize CD44/Pgp-1. Interest in these reagents increased with the finding that they totally inhibited production of lymphoid or myeloid cells in long-term bone marrow cultures. Further investigation has now revealed that hyaluronate is a potential ligand for CD44 and that hyaluronate recognition accounts for the adhesion between B lineage hybridoma and stromal cells. The hybridoma cells adhered to hyaluronate-coated plastic wells as well as to monolayers of stromal cells. The adhesion in both cases was inhibited by treatment with hyaluronidases, and did not require divalent cations. Addition of exogenous hyaluronate also diminished binding of lymphoid cells to stromal cells. One of several mAbs to Pgp-1/CD44 was particularly effective at blocking these interactions. Since hyaluronate and Pgp-1/CD44 were present on both cell types, experiments were done to determine the cellular location of interacting molecules required for the adhesion process. Treatment of lymphoid cells with an anti-Pgp-1/CD44 antibody was more inhibitory than antibody treatment of the stromal cells. Conversely, hyaluronidase treatment of stromal cells reduced subsequent binding more than treatment of the lymphoid cells. Adhesive interactions that involve hyaluronate and CD44 could contribute to a number of cell recognition processes, including ones required for normal lympho-hemopoiesis.
先前曾使用一种细胞黏附模型来筛选一系列单克隆抗体（mAb），随后发现这些抗体可识别CD44/Pgp-1。随着发现它们能完全抑制长期骨髓培养中淋巴细胞或髓细胞的产生，对这些试剂的兴趣增加。现在进一步的研究表明，透明质酸是CD44的潜在配体，并且透明质酸识别是B系杂交瘤与基质细胞之间黏附的原因。杂交瘤细胞既能黏附于包被透明质酸的塑料孔，也能黏附于基质细胞单层。在这两种情况下，黏附均被透明质酸酶处理所抑制，并且不需要二价阳离子。添加外源性透明质酸也会减少淋巴细胞与基质细胞的结合。几种针对Pgp-1/CD44的单克隆抗体之一在阻断这些相互作用方面特别有效。由于透明质酸和Pgp-1/CD44在两种细胞类型上均存在，因此进行了实验以确定黏附过程所需相互作用分子的细胞定位。用抗Pgp-1/CD44抗体处理淋巴细胞比处理基质细胞更具抑制作用。相反，用透明质酸酶处理基质细胞比处理淋巴细胞更能减少随后的结合。涉及透明质酸和CD44的黏附相互作用可能有助于许多细胞识别过程，包括正常淋巴细胞生成所需的过程。
