GROWTH REGULATION IN NORMAL AND TRANSFORMED PHAGOCYTES

单核巨噬细胞的增殖和分化 受一组名为集落的造血生长因子的调节- 刺激因子(CSF)。在小鼠体内，大多数巨噬细胞前体细胞 同时展示几种类型的脑脊液受体并对脑脊液做出反应 要么单独行动，要么联合行动。尽管他们看起来是多余的， 生物效应的重叠，CSF以分层和协调的方式发挥作用 如何控制巨噬细胞的增殖和分化。 受体结合分析表明，尽管CSF并不共享每个 其他的受体位置，它们可以诱导快速的瞬时下调 其他脑脊液受体。然而，尽管J774单核细胞样瘤细胞 展示多个脑脊液受体系统，它们不展示受体 在正常的对应物中看到的跨调制。我们的工作假说 是不同的脑脊液受体通过信号网络连接在一起 在造血过程中的增殖和分化过程 电池是耦合的。据认为，脑脊液与脑脊液之间的解偶联 造血细胞中的受体可能导致分化受阻和 白血病细胞的不受控制的增殖特征。要验证 这一假设，我们将首先研究相关的生化变化 正常人受体反式调节及其生物学意义 巨噬细胞及其白血病对应的J774细胞。接下来，我们将 受体-受体相互作用的生化基础研究 并确定导致白血病受体解偶联的原因 细胞。最后，我们将研究生物反应是否与 与受体的反式调节也在基因水平上受到调节。 这项建议的总体目标是更深入地了解 受体-受体相互作用的生物学意义及其作用 细胞增殖与分化过程中的相互作用 在造血细胞中。

The proliferation and differentiation of mononuclear phagocytes are regulated by a group of hemopoietic growth factors known as colony- stimulating factors (CSFs). In mouse, most macrophage precursor cells display several types of CSF receptors simultaneously and respond to CSFs either alone or in combination. Despite their seeming redundancy and overlap in biologic effects, CSFs act in a hierarchical and coordinated manner toward the control of macrophage proliferation and differentiation. Receptor binding assay indicates that although CSFs do not share each other's receptor sites, they can induce a rapid transient down-regulation of other CSF receptors. However, although J774 monocyte-like tumor cells display multiple CSF receptor systems, they do not exhibit the receptor trans-modulation seen in their normal counterparts. Our working hypothesis is that various CSF receptors are linked through a signaling network by which the processes of proliferation and differentiation in hemopoietic cells are coupled. It is thought that the un-coupling between CSF receptors in hemopoietic cells may lead to the arrested differentiation and uncontrolled proliferation characteristic of leukemic cells. To verify that hypothesis, we will first study the biochemical changes associated with receptor trans-modulation and their biologic significance in normal macrophages and their leukemic counterparts, J774 cells. Next, we will study the biochemical basis responsible for receptor-receptor interaction and determine the causes leading to receptor-uncoupling seen in leukemic cells. Finally, we will study whether the biologic responses associated with receptor trans-modulation are regulated at genetic levels as well. The overall objective of this proposal is to gain more insight into the biologic significance of receptor-receptor interaction and the role of this interaction in linking the processes of proliferation and differentiation in hemopoietic cells.