Bacterial lipopolysaccharide (LPS) is a potent and pleiotropic stimulus of immune cells. LPS has important clinical relevance because it has a direct role in the pathogenesis of Gram-negative bacterial infection. The lipid A moiety of LPS is responsible for the toxic effects of LPS. The identification of structural analogs and precursors of lipid A, which are apparently competitive antagonists of the biological actions of LPS, is strong evidence that the actions of LPS are mediated by a specific LPS receptor or family of receptors. Identification and analysis of these LPS receptors with LPS antagonists should help to define the pathways of cellular activation b~, LPS and lead to the development of novel anti-LPS strategies in the therapy of bacterial diseases.

Lipopolysaccharide (LPS or endotoxin), a complex glycolipid, is the major component of the outermost membrane of Gram-negative bacteria. There is much interest in LPS because it provides a potent and pleiotropic stimulus for immune cells, both in vitro and in t, ivo,'-, and because it has been implicated in the clinical syndrome of Gram-negative bacterial septic shock. Animals injected with purified LPS develop signs that mimic sepsis, and antibodies to LPS ameliorate Gram-negative bacterial shock in laboratory animals and in septic patientsL Structurally, LPS consists of a variable polysaccharide domain covalently bound to a diglucosaminebased acylated phospholipid, lipid A (Fig. 1) 4. Although the polysaccharide portion of LPS varies considerably, the lipid A domain is highly conserved between otherwise diverse strains of Gram-negative bacteria. Purified and synthetic preparations of lipid A have potent LPS agonist activity; thus, it appears that the lipid A portion of the molecule is responsible for most of the biological effects