ARGININE REGULATION OF CELL FUNCTION IN HEALING WOUNDS

组织损伤后的修复现象发生在一个 不同于其他细胞外体的环境 隔间 在其他特征中，伤口环境是 其定义为游离精氨酸浓度显著低于 比等离子体更高。 细胞外精氨酸的减少， 在氨基酸中是独一无二的，主要来自于 这种氨基酸的巨噬细胞在损伤部位。 最近 研究结果表明，改变精氨酸的可用性， 深刻地改变细胞的新陈代谢和功能， 对伤口愈合很重要 伤口培养 精氨酸缺乏培养基中的巨噬细胞导致 超氧化物（O2-）产生和吞噬作用。 研究使用 腹腔巨噬细胞表现出增强的O2-产生， 吞噬作用、蛋白质合成、乳酸产生和杀肿瘤 在精氨酸减少的条件下培养期间的活性 空房的 因此，伤口中的巨噬细胞不仅决定了 占主导地位的细胞外精氨酸浓度，但可能，通过 精氨酸利用率的调节，自动调节它们的状态 激活和功能。 还已知形成的产物 在精氨酸的催化过程中， （抑制呼吸和DNA合成）在其他细胞和 可能存在于伤口内的细胞因子（即：IL-1、TNF 和γ-干扰素）可诱导成纤维细胞对精氨酸的催化作用 导致代谢抑制的途径。 在 此外，淋巴细胞增殖在精氨酸- 缺乏培养物。 因此，精氨酸可能参与 调节细胞群的代谢和功能 在伤口愈合中的重要性在于：1）其 可用性，2）其代谢副产物的影响，以及 3)精氨酸及其代谢产物与细胞因子的相互作用 在伤口里。 本研究的目的是 建议是调查这些潜在机制的作用 调节细胞代谢和功能， 炎症细胞 这些研究将在培养的 从皮下植入的聚乙烯醇获得的细胞 老鼠体内的海绵 精氨酸在细胞凋亡中的作用 伤口细胞功能的调节可以提供更好的 了解炎症和修复的整个过程。

The reparative phenomena that follow tissue injury occur within an environment that is different from other extracellular body compartments. Among other characteristics, the wound milieu is defined by a free arginine concentration that is markedly lower than that of plasma. This reduction in extracellular arginine, unique among the amino acids, results primarily from the catabolism of this amino acid by macrophages at the site of injury. Recent findings have demonstrated that altered arginine availability can profoundly modify the metabolism and function of cells that are important to the process of wound healing. Culture of wound macrophages in arginine deficient media results in increased superoxide (O2-) production and phagocytosis. Studies using peritoneal macrophages demonstrated enhanced O2- production, phagocytosis, protein synthesis, lactate production and tumoricidal activity during culture in conditions of reduced arginine availability. Thus, macrophages in wounds not only determine the prevailing extracellular arginine concentration, but may, through the modulation of arginine availability, auto-regulate their state of activation and function. It is also known that products formed during the catabolism of arginine can induce metabolic alterations (inhibition of respiration and DNA synthesis) in other cells and that cytokines likely to be present within wounds (ie: IL-1, TNF and gamma-IFN) can induce the catabolism of arginine by fibroblasts through pathways shown to result in metabolic inhibition. In addition, lymphocyte proliferation is suppressed in arginine- deficient cultures. Thus, arginine may participate in the regulation of the metabolism and function of cellular populations important in wound healing by virtue of: 1) alterations in its availability, 2) effects of the by-products of its metabolism and 3) interactions between arginine or its metabolites with cytokines present within the wound. The objective of the studies in this proposal is to investigate the role of these potential mechanisms in the regulation of cellular metabolism and function in inflammatory cells. These studies will be performed in cultured cells obtained from subcutaneously implanted polyvinyl alcohol sponges in the rat. Elucidation of the role of arginine in the regulation of wound cell function may provide a better understanding of the overall process of inflammation and repair.