HUMAN BLOOD MONOCYTE RECEPTOR EXPRESSION AND MODULATION

单核/巨噬细胞Fc(Ig G)和C3受体在宿主防御中起重要作用 在几种血液病的病理生理学中。增强了 它们的活动促进了这些细胞消除 微生物。抑制它们的活性可以改善临床状态 患有自身免疫性溶血性贫血和血小板减少症的患者。我们的 这项研究计划的目标是描述生物化学、免疫学 以及调节这些基因表达的药物机制 感受器。 我们将通过分析结合分析来研究Fc(Ig G)和C3受体的表达 由1)放射性标记的Ig G和C3b单体的单核/巨噬细胞和 低聚物和2)包被一定数量的Ig G、C3b和 C3bi。我们将确定C3b受体的扰动对 单体和单核/巨噬细胞结合部位的数量和亲和力 低聚免疫球蛋白。我们还将检测Fc(Ig G)受体的作用 单核/巨噬细胞结合数量和亲和力的扰动 C3b单体和二聚体的位置。我们将定义一种机制， 合成的N-甲酰寡肽，类似于细菌产生的， 增强Fc(Ig G)受体活性及其对C3b的影响 受体表达。我们还将分析一项重要的 内源性介质组胺对这些基因表达的影响 表面受体。我们的初步数据表明，组胺确实会改变 Fc(Ig G)受体表达。我们将确定通过哪些机制 血液病常用的药物--皮质类固醇 疾病，调节单核/巨噬细胞Fc(IgG)和C3受体的表达。 我们将研究类固醇类似物增强或抑制 这些受体的表达。在这些研究中，我们还将使用我们的 检测巨噬细胞免疫球蛋白Fc和补体C3调节的活体动物模型 感受器活性。最后，我们将检查更改的能力 单核/巨噬细胞膜胆固醇/磷脂对铁(IgG)的调节作用 和C3b受体的表达。这些研究应该有助于 了解单核细胞和巨噬细胞受体的作用机制 在人类疾病中，表达会发生变化。此外，它们应该是 有助于开发调节这种受体表达的方法 体外和体内。

Monocyte/macrophage Fc (IgG) and C3 receptors are important in host defense and in the pathophysiology of several hematologic diseases. Enhancement of their activity facilitates the ability of these cells to eliminate microorganisms. Inhibition of their activity improves the clinical status of patients with autoimmune hemolytic anemia and thrombocytopenia. Our goals in this research proposal are to delineate biochemical, immunologic and pharmacologic mechanisms which modulate the expression of these receptors. We will study Fc (IgG) and C3 receptor expression by analyzing the binding by monocytes/macrophages of 1) radiolabeled IgG and C3b monomer and oligomer and 2) erythrocytes coated with defined amounts of IgG, C3b and C3bi. We will determine the effect of C3b receptor perturbation on the number and affinity of monocyte/macrophage binding sites for monomeric and oligomeric IgG. We will also examine the effect of Fc (IgG) receptor perturbation on the number and affinity of monocyte/macrophage binding sites for C3b monomer and dimer. We will define the mechanisms by which a synthetic N-formyl oligopeptide, similar to that produced by bacteria, augments Fc (IgG) receptor activity and determine its effect on C3b receptor expression. We will also analyze the effect of an important endogenously derived mediator, histamine, on the expression of these surface receptors. Our preliminary data indicate that histamine does alter Fc (IgG) receptor expression. We will determine the mechanisms by which corticosteroids, commonly utilized pharmacologic agents in hematologic disease, modulate monocyte/macrophage Fc (IgG) and C3 receptor expression. We will examine the capacity of steroid analogues to enhance or inhibit the expression of these receptors. In these studies we will also use our in vivo animal model to examine modulation of macrophage Fc (IgG) and C3 receptor activity. Finally, we will examine the capacity of alterations in monocyte/macrophage membrane cholesterol/phospholipid to modulate Fe (IgG) and C3b receptor expression. These studies should be helpful in understanding the mechanisms by which monocyte and macrophage receptor expression is altered in human disease. Furthermore, they should be helpful in developing approaches to modulate such receptor expression in vitro and in vivo.