HUMORAL FACTORS IN INFLAMMATION

血清过敏毒素的化学定义进展迅速， 近年 结构-功能研究建议在这里进一步 确定这些因子的活性部位和作用机制。 过敏毒素是由过敏原释放的低分子量多肽。 在激活过程中的补体成分。 完成小学 三种人过敏毒素的结构（例如，C3 a、C5 a和C5 a）具有 最近在我的实验室里被阐明了。 定量数据也 收集了与这些相关的许多生物活动， 纯化的过敏毒素，旨在评估其作用， 体外和体内。 另一种体液因子，人C3 e，将被 进行了化学和生物学的检测。 最近有人提出， C3 e可能是抑制丝裂原诱导淋巴细胞增殖的C3衍生因子 胚细胞发生 如果C3 e被证明具有免疫调节活性， 除了白细胞动员活性，那么这个因素将是 被认为是宿主防御中非常重要的因素。 过敏毒素 已经显示在肺组织中引起急性反应。 严重肺 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。 我们现在认识到， 将过敏毒素引入肺组织的气道侧， 肺部结构的外观发生了巨大变化。 复杂 脂质介质的释放是过敏毒素作用于 肺组织 据报道，C3 a过敏毒素释放血管胺， 已知C5 a释放血管胺和白三烯。 这项建议的一个主要重点是检查过敏毒素的潜力 用于在肺组织中诱导由反复损伤引起的慢性损伤。 纯化的过敏毒素将反复给予气道和 和肺组织的血管侧， 将通过组织化学和组织学检查评估效果。 将利用过敏毒素的特异性抑制剂 灭活剂（羧肽酶N），以及抗组胺药和抑制剂 花生四烯酸途径在评估过敏毒素在 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.