OSTEOCLASTS & GIANT CELLS--MECHANISMS & FUNCTIONS

本建议的长期目标是：1）阐明机制 以及单核吞噬细胞（MNP）融合的调节，导致 破骨细胞和巨细胞的形成。 2)表征 正常和病理性多核化的功能后果 骨吸收和宿主防御机制参与炎症 反应和肿瘤。 为实现这些目标而采取的战略是基于同时使用 两种方法相辅相成：1）第一种方法 集中在细胞和分子基础上的特定趋势 MNP谱系的细胞形成多核体。 这种方法将更多 具体涉及检测、表征和动力学 分析新的质膜和可溶性抗原。 2)第二 方法侧重于当地微环境在 单核细胞融合机制的诱导和调控 前体（MNP）。 将搜索激动剂和拮抗剂因子 和分析 这两种方法密切相互作用， 对质膜蛋白组成的局部因素也将是 研究了 将继续对体内诱导的破骨细胞进行平行研究 和巨细胞分析和比较它们各自的抗原 决定因素使用免疫电镜技术。 从长远来看，这些研究可能对 了解巨噬细胞融合对骨的功能影响 再吸收和宿主防御机制。

The long term goals of this proposal are: 1) to elucidate the mechanisms and the regulation of the fusion of mononuclear phagocytes (MNP) leading to the formation of both osteoclasts and giant cells. 2) to characterize the functional consequences of multinucleation in both normal and pathological bone resorption and in the host defense mechanisms involved in inflammatory reactions and tumors. The strategy adopted to reach these goals is based on the simultaneous use of two approaches which complement each other: 1) the first approach focuses upon the cellular and molecular basis for the particular tendency of cells of the MNP lineage to form polykaryons. This approach will more specifically involve the detection, the characterization and the kinetic analysis of new plasma membrane and soluble antigens. 2) the second approach focuses upon the role of the local microenvironment in the induction and the regulation of the fusion mechanism of the mononuclear precursors (MNP). Both agonist and antagonist factors will be searched for and analyzed. These two approaches closely interact in that the effects of local factors on the plasma membrane protein composition will also be studied. Parallel studies will be continued on in vivo induced osteoclasts and giant cells analyzing and comparing their respective antigenic determinants using immunoelectron microscopy techniques. In the long run, these studies may be of critical importance in the understanding of the functional implications of macrophage fusion is bone resorption and host defense mechanisms.