Fenton M J, Golenbock D T
The Pulmonary Center, Boston University School of Medicine, MA 02118, USA.
J Leukoc Biol. 1998 Jul;64(1):25-32. doi: 10.1002/jlb.64.1.25.
Macrophage activation by gram-negative lipopolysaccharide (LPS) has been extensively studied in an attempt to define the mechanisms that underlie innate immunity against bacterial pathogens. Dysregulation of these same mechanisms contributes to the pathophysiological consequences of bacterial sepsis. The biological actions of LPS are mediated, at least in part, by both LPS-binding proteins and LPS receptors. Several LPS receptors (CD14, the macrophage scavenger receptor, and the beta2 integrins), as well as the serum LPS-binding protein LBP, have been cloned and studied in detail. In addition, insights gained through the use of LPS antagonists have led to a better understanding of a molecule believed to function in conjunction with LPS receptors to transduce signals from the membrane to the cytosol. More recently, the use of knockout mice has greatly expanded our knowledge of the biology of LPS receptors and binding proteins. This review will summarize various phenotypes of mice that lack genes encoding CD14, the scavenger receptor, and LBP. These knockout mice have revealed several unexpected features of LPS action in vivo. Together, these animal models may provide a means to develop and evaluate novel therapeutic approaches to the control of endotoxin shock.
革兰氏阴性菌脂多糖（LPS）激活巨噬细胞的过程已得到广泛研究，旨在确定针对细菌病原体的固有免疫的潜在机制。这些相同机制的失调会导致细菌性败血症的病理生理后果。LPS的生物学作用至少部分是由LPS结合蛋白和LPS受体介导的。几种LPS受体（CD14、巨噬细胞清道夫受体和β2整合素）以及血清LPS结合蛋白LBP已被克隆并进行了详细研究。此外，通过使用LPS拮抗剂获得的见解使人们对一种被认为与LPS受体协同作用以将信号从细胞膜传导至细胞质的分子有了更好的理解。最近，基因敲除小鼠的使用极大地扩展了我们对LPS受体和结合蛋白生物学的认识。本综述将总结缺乏编码CD14、清道夫受体和LBP基因的小鼠的各种表型。这些基因敲除小鼠揭示了LPS在体内作用的几个意外特征。总之，这些动物模型可能为开发和评估控制内毒素休克的新治疗方法提供一种手段。
