REGULATION OF MACROPHAGE ANGIOGENIC ACTIVITY

巨噬细胞诱导血管生成， 血管形成在许多重要的 病理生理过程，但调节机制， 这种重要功能的控制表达仍然知之甚少。 本研究的总体目标是利用体细胞杂种 研究调节表达的机制， 巨噬细胞血管生成活性（AA）。 具体目的是：（1）检验假设，即能力 巨噬细胞表达AA是一种隐性性状， 未激活或未分化的反式作用抑制 巨噬细胞，（2）以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）与新生毛细血管 （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。 将细胞与聚乙二醇（PEG-1000）融合， 杂交种将在HAT或HAT-Oubain中生长和选择 介质 将在以下条件下测定杂交体调节的培养基的AA： 鸡胚绒毛尿囊膜（CAM）和大鼠角膜。 增殖、定向迁移和PA活性将是 用牛肾上腺毛细血管内皮细胞培养物测定 细胞（BCE）的直接细胞计数，测量迁移下 琼脂糖，并通过测定125 I- 标记的纤维蛋白平板。 在杂种中再诱导AA将是 在细胞暴露于脂多糖（LPS）后进行评价。 染色体携带参与诱导的基因， AA的抑制将通过核型分析来确定 胰蛋白酶/Giemsa G显带中期染色体。 这项研究的结果将提供更深入的了解（1）如何 AA的表达在分化过程中受到控制， 巨噬细胞的活化，（2） AA在肿瘤细胞中的不受调节的表达和（3）允许 新分子的开发和最终实现 治疗疾病过程的方法， 微血管增生已被证明有助于其 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.