Analysis of CD29/VLA integrin in T cell immune regulation and its clinical significance

附着于骨髓（BM）基质细胞对于B细胞祖细胞（pro-B）的正常生长和发育至关重要。然而，接触促进pro-B细胞增殖的分子机制尚未完全了解。本研究发现，与正常骨髓基质细胞和KM 102细胞贴附后，Reh细胞的生长明显增强，而与KM 102细胞贴附后，Reh细胞的生长明显增强。用抗整合素β 1或α 5单克隆抗体（mAb）预处理Reh细胞，而不是α 4或ICAM-1 mAb，消除了这种增殖增强。此外，间质附着导致细胞周期G（1）期缩短，cdk 2活性显著增加，cdk抑制剂p27-GST蛋白降解，p27（Kip 1）蛋白水平降低。此外，通过固定化抗体的α 5固相交联也导致细胞外信号调节（ERK）-2激酶磷酸化，cdk 2活性增加，p27（Kip 1）蛋白水平降低，以及通过用PD 98059处理抑制的增殖增强，整合素α 5 β 1介导的基质接触通过ERK-2的活化促进B细胞祖细胞的增殖，其反过来调节细胞周期调节机制，包括cdk 2活性的诱导和p27（Kip 1）的降解，并促进细胞周期进程的G（1）期的加速。

Attachment to bone marrow(BM)stromal cells is crucial for the normal growth and development of B-cell progenitors(pro-B). However, the molecular mechanisms by which contact facilitates the proliferation of pro-B cells are not completely understood. This study was performed to investigate this interaction.Attachment to both KM102 and normal BM stromal cells significantly promoted the growth of Reh cells. Pretreatment of Reh cells with anti-integrin beta1 or alpha5 monoclonal antibody(mAb), but not alpha4 or ICAM-1 mAb, abrogated this enhancement of proliferation. Furthermore, stroma attachment resulted in shortening of the G(1)phase of cell cycle, significant increases cdk2 activity, degradation of cdk inhibitor p27-GST protein, and decrease in levels of p27(Kip1)protein. In addition, solid-phase cross-linking of alpha5 via immobilized antibody also resulted in extracellular signal-regulated(ERK)-2 kinase phosphorylation, increase in cdk2 activity, decrease in levels of p27(Kip1)protein, and enhanced proliferation that was inhibited by treatment with PD98059, a specific ERK inhibitor.Integrin alpha5beta1-mediated stroma contact promotes the proliferation of B-cell progenitors through the activation of ERK-2, which in tum modulates cell cycle regulation machinery including induction of cdk2 activity and degradation of p27(Kip1)and contributing to acceleration of the G(1)phase of cell cycle progression.