RECOGNITION OF BACTERIAL-ENDOTOXINS BY RECEPTOR-DEPENDENT MECHANISMS

This chapter discusses recent progress in identifying the cellular molecules that function as lipopolysaccharide (LPS) receptors. It focuses on data obtained with cells of monocytic origin and findings derived from studies of other cell types for illustration of specific points. The importance of recognizing LPS in responding to gram-negative infection is uniquely illustrated by the LPS-resistant mouse strain, C3H/HeJ, refractory to the toxic effects of LPS but hypersensitive to gram-negative infections. Thus, the inability to respond to LPS compromises host defenses against gram-negative sepsis whereas an uncontrolled response to LPS results in shock, diffuse intravascular coagulation, and multiorgan failure. LPS is a structural component of the outer membrane of all gram-negative bacteria. LPS consists of two chemically dissimilar domains—namely, (1) the hydrophilic, polysaccharide core and O-antigen structures and (2) a hydrophobic region known as lipid A. The chapter presents a schematic structure for LPS from Escherichia coli and the detailed chemical structure of lipid A. Research performed during the past years has provided a considerable amount of evidence to support the contention that the initial interaction of LPS with cells is mediated by distinct plasma membrane proteins. Some of these interactions are involved in removal and eventual degradation of LPS, whereas others may play a critical role in transmembrane signaling. © 1993, Academic Press Inc.