REGULATION OF MACROPHAGE ANGIOGENIC ACTIVITY

巨噬细胞诱导血管生成，新的毛细血管形成过程 血管形成中的一些重要因素 病理生理过程还没有调节机制， 对这一重要功能的调控表达仍然知之甚少。 这项研究的总体目标是使用体细胞杂交 探讨其调控基因表达的机制。 巨噬细胞血管生成活性(AA)。 具体目标是：(1)检验假设能力 巨噬细胞表达AA是一种隐性性状，受 未激活或未分化的反式作用抑制 巨噬细胞，(2)确定是否抑制和重新表达 AA与某些内皮细胞的抑制和再表达平行 细胞功能(增殖、定向迁移和 纤溶酶原激活物(PA)活性)与新的毛细血管相关 形成，(3)确定AA的反式作用抑制是否可以 被激活的巨噬细胞已知的刺激逆转，以及(4) 确定携带参与基因的特定染色体。 巨噬细胞AA的诱导和抑制。 细胞将与聚乙二醇(聚乙二醇1000)和 杂交种将在HAT或HAT-OBAIN中种植和选择 5~6成熟。混合培养基将被检测AA On 鸡胚绒毛尿囊膜(CAM)和大鼠角膜。 增殖、定向迁移和PA活性将 牛肾上腺毛细血管内皮细胞培养法检测 细胞(BCE)通过直接细胞计数，测量 琼脂糖凝胶和分析放射性释放~(125)I- 标有纤维蛋白板。在杂交种中重新诱导AA将是 在细胞暴露于脂多糖(LPS)后进行评估。 携带参与诱导的基因的染色体和 对AA的抑制将通过核型分析来确定 胰酶/Giemsa G显带中期染色体。 这项研究的结果将提供更多关于(1)如何 AA在分化和分化过程中的表达受到控制 巨噬细胞的激活，(2) AA在肿瘤细胞中的不受调控的表达和(3)允许 新型分子材料的发展和最终实现 在以下情况下处理疾病过程的方法 微血管增殖已被证明有助于其 发病机制。

Macrophages induce angiogenesis, the process of new capillary blood vessel formation in a number of important pathophysiological processes yet the regulatory mechanisms that control expression of this vital function are still poorly understood. The overall objective of this study is to use somatic cell hybrids to investigate the mechanisms which regulated expression of macrophages angiogenic activity (AA). The specific aims are: (1) to test the hypothesis that the ability of macrophages to express AA is a recessive trait, subject to trans-acting suppression by unactivated or undifferentiated macrophages, (2) to determine if suppression and re-expression of AA parallels suppression and re-expression of certain endothelial cell functions (proliferation, directional migration and plasminogen activator (PA) activity) associated with new capillary formation, (3) to determine if trans-acting suppression of AA can be reversed by stimuli known to activated macrophages and (4) to identify specific chromosomes carrying genes involved in the induction and suppression of macrophages AA. Cells will be fused with polyethylene glycol (PEG-1000) and hybrids will be grown and selected in HAT or HAT-Oubain medium. Media conditioned by hybrids will be assayed for AA on the chick chorioallantoic membrane (CAM) and in the rat cornea. Proliferation, directional migration and PA activity will be assayed with cultures of bovine adrenal gland capillary endothelial cells (BCE) by direct cell counts, measuring migration under agarose and by assaying release of radioactivity from 125I- labelled fibrin plates. Re-induction of AA in hybrid will be evaluated following exposure of cells to lipopolysaccharide (LPS). Chromosomes carrying genes involved in the induction and suppression of AA will be determined by karyotyping trypsin/Giemsa G banded metaphase chromosomes. The results of this study will provide greater insight into (1) how expression of AA is controlled during differentiation and activation of macrophages, (2) the mechanism underlying the unregulated expression of AA in neoplastic cells and (3) allow for the development and eventual implementation of novel molecular approaches for the treatment of disease processes when microvascular proliferation has been shown to contribute to their pathogenesis.