RATS ARE NOT PEOPLE AND PEOPLE ARE NOT HORSES: COMPARATIVE ASPECTS OF ENDOTOXEMIA

摘要

Richard Pfeifer first characterized endotoxin in the 1890s as a toxin that was an integral part of gram-negative bacteria that was distinctly different from actively secreted heat labile exotoxins.1 Endotoxin comprises approximately 75% of the outer cell membrane of gram-negative bacteria and serves as a structural permeability barrier. Pfeifer's original observations were correct: bacteria do not actively secrete endotoxin. Rather, when gram-negative bacteria multiply or lyse upon bacterial cell death, endotoxin is released from the outer cell membrane. Endotoxin consists of three structural domains: a highly variable outer polysaccharide "O-antigenic" region, a core region consisting mostly of monosaccharides, and the highly conserved toxic moiety, lipid A. Variation in the number, length, saturation, and position of fatty acids on the glucosamine disaccharide backbone of lipid A confers its degree of toxicity. Endotoxin has been evolutionarily conserved as a pathogen associated molecular pattern that is immediately recognized by the innate immune system that subsequently initiates a series of inflammatory signals that serve to warn of and control the bacterial invasion. However, mammalian species vary considerably in their ability to recognize the presence of endotoxin. The main purpose of this discussion is to review what is known about endotoxemia among species, with particular emphasis on comparative aspects between human beings and horses.