HUMORAL FACTORS IN INFLAMMATION

血清过敏性毒素的化学定义在#年进展迅速。 最近几年。提出了结构-功能研究的建议，以进一步 定义这些因子的活性部位和作用机制。 过敏性毒素是一种小分子多肽，从 在激活过程中补充成分。完成主要任务 三种人类过敏性毒素(如C3a、C5a和C5a)的结构 最近在我的实验室里被阐明了。量化数据也一直在 收集了许多与这些相关的生物活动 纯化的过敏性毒素的检测旨在评估它们在 体外和体内。另一个体液因素，人类C3E，将是 对其进行了化学和生物检验。最近有人建议说 C3E可能是抑制有丝分裂原诱导的淋巴细胞的C3衍生因子 胚泡发生。如果C3E被证明具有免疫调节活性，在 除了白细胞的动员活性，那么这个因子就会 被认为是宿主防御中的一个非常重要的因素。过敏性毒素 已被证明能在肺组织中引起急性反应。重症肺 涉及补体激活片段的损伤从未在 对肺组织的慢性影响的ERMS。我们现在意识到 过敏性毒素进入肺组织的气道侧引起 肺部建筑外观的戏剧性变化。复合体 脂质介质的释放是过敏毒素作用的直接结果。 肺组织。据报道，C3a过敏毒素释放血管胺和 前列腺素，而C5a已知可以释放血管胺和白三烯。 这项提议的一个主要焦点是检查过敏毒素的潜力。 因反复侮辱而导致肺组织慢性损伤。 纯化的过敏性毒素将被重复地注射到两个呼吸道 和肺组织的血管侧，以及即时和长期的 效果将通过组织化学和组织学检查进行评估。 将利用特定的过敏性毒素抑制剂 灭活剂(羧基肽酶N)，以及抗组胺药物和抑制剂 花生四烯酸途径在评估过敏毒素在糖尿病中的作用 肺损伤。

Chemical definition of serum anaphylatoxins has progressed rapidly in recent years. Structure-function studies are proposed here to further define the active site and mechanisms of action of these factors. Anaphylatoxins are low molecular weight polypeptides released from complement components in the course of activation. Complete primary structures of three human anaphylatoxins (e.g., C3a, C5a and C5a) have recently been elucidated in my laboratory. Quantitative data has also been collected regarding numerous biological activities associated with these purified anaphylatoxins in assays designed to assess their actions both in vitro and in vivo. An additional humoral factor, human C3e, will be examined both chemically and biologically. Recently it was suggested that C3e may be the C3-derived factor that inhibits mitogen-induced lymphocyte blastogenesis. If C3e proves to have immunoregulatory activities, in addition to leukocyte mobilizing activity, then this factor will be recognized as a very important factor in host defense. The anaphylatoxins have been shown to elicit acute responses in lung tissue. Severe lung injury involving complement activation fragments has never been examined in erms of chronic effects on pulmonary tissue. We now realize that introduction of anaphylatoxins to the airway side of lung tissue causes dramatic changes in the appearance of the lung's architecture. Complex lipid mediators are released as a direct result of anaphylatoxin action on pulmonary tissue. The C3a anaphylatoxin reportedly release vasoamines and prostaglandins while C5a is known to release vasoamines and leukotrienes. A main focus of this proposal is to examine the potential of anaphylatoxins for inducing chronic damage in pulmonary tissue from repeated insult. Purified anaphylatoxins will be administered repeatedly to both the airway and vascular sides of the lung tissue and both immediate and long-term effects will be assessed by histochemical and histological examination. Advantage will be taken of specific inhibitors of the anaphylatoxin inactivator (carboxypeptidase N), as well as antihistamines and inhibitors of the arachidonate pathways in estimating the role of anaphylatoxins in lung damage.