Antibodies to the beta 1-integrin chain, CD44, or ICAM-3 stimulate adhesion of blast colony-forming cells and may inhibit their growth.
Antibodies to the beta 1-integrin chain, CD44, or ICAM-3 stimulate adhesion of blast colony-forming cells and may inhibit their growth.
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β1-整合素链、CD44 或 ICAM-3 的抗体会刺激母细胞集落形成细胞的粘附，并可能抑制其生长。
作者：
R. A. Oostendorp;E. Spitzer;G. Reisbach;Peter Dörmer
早期造血祖细胞粘附骨髓基质细胞（BMSCs）主要通过vca -4/VCAM-1相互作用。然而，许多粘附分子是由这些细胞类型表达的。细胞粘附分子不仅介导粘附；有些还能触发细胞信号事件。这些信号可以由几种抗黏附分子抗体诱导。在这项研究中，我们研究了几种这样的刺激抗体对α L （CD11a）、α 4 （CD49d）和β 1 （CD29）整合素链、ICAM-3 （CD50）、CD34、CD44和CD45的作用。所有抗体均与cd34阳性骨髓细胞有强烈反应，但只有针对β 1整合素（TS2/16, Lia1/2）或CD44 （NKI-P2）的抗体与骨髓细胞有反应。为了测试这些抗体刺激黏附相互作用的能力，我们分析了它们对基质黏附母细胞集落形成细胞（Bl-CFCs）的影响。我们发现，与同型对照处理的细胞相比，TS2/16（抗β 1整合素）、NKI-P2（抗cd44）和152-2D11（抗icam -3）增强了BM单核细胞对基质的粘附（ts2 /16:3.4倍，NKI-P2: 3.8倍，152-2D11: 2.6倍）。随着基质贴壁细胞的增加，第5-7天的blast菌落数量分别增加了3.8倍、2.6倍和1.9倍。一种针对CD29的抗体：Lia1/2强烈抑制blast菌落的形成，这种效果至少部分是由其生长抑制活性引起的。在测试的其他抗体中，没有一种显示出生长调节活性。我们以前发现，Bl-CFCs强烈依赖于vca -4和VCAM-1。然而，在TS2/16或152- 2d11处理的培养物中，我们不仅观察到这些，还观察到vla -5依赖的粘附相互作用。相反，VLA-5似乎不参与nki - p2处理的培养。我们的数据表明，β 1-整合素介导的相互作用参与了Bl-CFCs的生长。此外，β 1-整合素、CD44和ICAM-3介导的相互作用差异调节了vla4 -和vla5依赖性祖细胞/BMSC相互作用。
Early hematopoietic progenitor cells adhere to bone marrow stromal cells (BMSCs) mainly through VLA-4/VCAM-1 interactions. However, many adhesion molecules are expressed by these cell types. Cell adhesion molecules not only mediate adhesion; some are also capable of triggering cellular signaling events. These signals can be induced by several anti-adhesion molecule antibodies. In this study, we investigated the effects of several of such stimulatory antibodies against alpha L (CD11a), alpha 4 (CD49d), and beta 1 (CD29) integrin chains, ICAM-3 (CD50), CD34, CD44, and CD45. All antibodies reacted strongly with CD34-positive bone marrow (BM) cells, but only those against beta 1 integrin (TS2/16, Lia1/2) or CD44 (NKI-P2) reacted with BMSCs. To test the ability of these antibodies to stimulate adhesive interactions, we analyzed their effect on stroma-adherent blast colony-forming cells (Bl-CFCs). We found that TS2/16 (anti-beta 1 integrin), NKI-P2 (anti-CD44), and 152-2D11 (anti-ICAM-3) enhanced adhesion of BM mononuclear cells to stroma (TS2/16:3.4-fold, NKI-P2: 3.8-fold, 152-2D11: 2.6-fold) when compared with isotype-control-treated cells. The increase in stroma-adherent cells was accompanied by an increase in Day 5-7 blast colonies of 3.8-, 2.6-, and 1.9-fold, respectively. One antibody against CD29:Lia1/2 strongly inhibited the formation of blast colonies, an effect that was at least partially caused by its growth-inhibitory activity. Of the other antibodies tested, none displayed growth-modulatory activity. We have found previously that Bl-CFCs depend strongly on VLA-4 and VCAM-1. However, in TS2/16- or 152-2D11-treated cultures, we observed not only these, but also VLA-5-dependent adhesive interactions. In contrast, VLA-5 did not appear to be involved in NKI-P2-treated cultures. Our data indicate that interactions mediated by beta 1-integrins are involved in the growth of Bl-CFCs. Furthermore, interactions mediated by beta 1-integrins, CD44, and ICAM-3 differentially modulate VLA-4- and VLA-5-dependent progenitor/BMSC interactions.