BIOCHEMICAL PARAMETERS OF LPS-INITIATED HOST RESPONSE

多种生理、病理和免疫活性 细菌内毒素(脂多糖)已经有了很好的文献记载。 如此广泛的活动的一个主要原因是几乎 这些强效细菌产物的无处不在的相互作用能力 主机防御系统。现在有大量的证据表明 脂多糖大分子的脂类A区对其表达起关键作用 内毒素的生物活性。然而，这个问题的复杂性 组成内毒素大分子的亚基结构直到最近才 得到了充分的赞赏。这个实验室的最新证据提供了 富含脂质A(R-内毒素)亚单位在中介中起主导作用的证据 提出了内毒素的效应和实验来检验内毒素的有效性 这一假说是通过制备具有高度内毒素的大分子 定义的亚基组成。此外，亦建议进行研究，以研究 假定的R-内毒素亚基需要AS的生化基础 通过它们与哺乳动物细胞膜的相互作用进行评估。我们和其他人 推测脂多糖的非特异性疏水相互作用(脂蛋白A) 细胞膜有助于淋巴细胞的激活和 内毒素刺激巨噬细胞。这个实验室最近的一些实验已经 显示R-内毒素亚基与淋巴细胞选择性结合。 最后，建议从生物化学和生物化学两个方面来定义评价。 从生物学上讲，细菌释放的内毒素大分子 与宿主防御系统的相互作用，特别是血清补体 系统和吞噬巨噬细胞。到目前为止我们的实验已经 这表明，在这两个系统中，都有选择性地释放内毒素 亚基受这些宿主防御系统的影响，这很可能决定了 它们的生物活性的表达。这些集体实验旨在 确定细菌内毒素与宿主中介系统的相互作用 将提供有关以下各项贡献的基本信息 生物活性大分子降压散布 革兰氏阴性患者的血管内凝血特点 败血症。

The multiple physiological, pathological and immunological activities of bacterial endotoxins (lipopolysaccharides, LPS) have been well documented. A primary reason for this broad spectrum of activities is the almost ubiquitous capacity of these potent bacterial products to interact with host defense systems. There is now abundant evidence which indicates that the lipid A region of the LPS macromolecule is critical for the expression of biological activity of endotoxin. However, the complexity of the subunit structures which comprise the LPS maacromolecule has only recently been fully appreciated. Recent evidence from this laboratory has provided evidence for a dominant role for lipid A rich (R-LPS) subunits in mediating the effects of LPS and experiments are proposed to test the validity of this hypothesis by the preparation of LPS macromolecules with highly defined subunit composition. Studies are also proposed to examine the biochemical basis for the postulated requirement for R-LPS subunits as assessed by their interaction with mammalian cell membranes. We and others have postulated that non-specific hydrophobic interactions of LPS (lipid A) with cell membranes contributes to the activation of lymphoid cells and macrophages by LPS. Some recent experiments from this laboratory have demonstrated selective association of R-LPS subunits with lymphocytes. Finally, it is proposed to define an evaluate both biochemically and biologically the LPS macromolecules released from bacteria following their interaction with host defense systems, particularly the serum complement system and the phagocytic macrophage. Our experiments to date have suggested that, in both of these systems a selective release of LPS subunits is effected by these host defense systems which may well dictate their expression of biological activity. These collective experiments to define the interaction of bacterial endotoxins with host mediation systems will provide fundamental information on the contribution of these biologically active macromolecules to the hypotension and disseminated intravascular coagulation characteristic of patients with gram negative sepsis.