Endotoxin-Cell-Membrane Interactions Leading to Transmembrane Signaling

Abstract

It has been approximately 100 years since endotoxins were first recognized as bacterial products that were distinct from exotoxins (Pfeiffer, 1892). In contrast to these latter toxins, which are synthesized and secreted most prominently by gram-positive bacteria (but some by gram-negative), endotoxins are unique to gram-negative organisms. They normally exist as an integral and functional component of the bacterial outer cell membrane. When released from the bacteria, these endotoxins appear to have an almost limitless capacity to bind to, interact with, and, in many cases, rather significantly perturb mammalian cells. Such perturbations may result in an equally broad spectrum of varying responses that are elicited in man and other animals (Milner et al., 1971). The net consequences of such endotoxin-cell interactions, under some circumstances, are exceedingly beneficial to the host, as in the case of endotoxin-induced tumor regression and/or necrosis, or enhancement of immune responsiveness of the host to heterologous antigens (reviewed in Morrison and Ryan, 1979). In contrast, other endotoxin-cell interactions lead to responses which produce profoundly deleterious effects on host tissues, resulting in disease and even in death (reviewed in Morrison and Ulevitch, 1978). The various factors that interact to regulate these contrasting host responses remain as an area of considerable scientific interest and research effort.