Synthetic and natural Escherichia coli free lipid A express identical endotoxic activities

Abstract

The recently chemically synthesized Escherichia coli lipid A and the natural free lipid A of E. coli were compared with respect to their endotoxic activities in the following test systems: lethal toxicity, pyrogenicity, local Shwartzman reactivity, Limulus amoebocyte lysate gelation capacity, tumour necrotizing activity, B cell mitogenicity, induction of prostaglandin synthesis in macrophages, and antigenic specificity. It was found that synthetic and natural free lipid A exhibit identical activities and are indistinguishable in all tests.Lipopolysaccharides (endotoxins) of gram-negative bacteria which consist of a heteropolysaccharide and a lipid component (termed lipid A) elicit multiple acute pathophysiological effects such as fever, lethality, Shwartzman reactivity, macrophage and B-lymphocyte activation, and other activities [I]. In 1954 it was proposed that for the induction of these effects the polysaccharide portion is dispensable and that the lipid A component represents the active center responsible for the endotoxic properties of lipopolysaccharides [2]. Evidence for this was then obtained in numerous investigations [2 -41 and this concept is now generally accepted.The chemical structure of the lipid A component of several enterobacterial lipopolysaccharides has been analysed during recent years in great detail (for reviews see [5, 61) and it was recognized that lipid A of Escherichiu coli possesses a comparatively simple structure. Free E. coli lipid A consists of a 8(1-6)-linked D-glucosamine disaccharide which is substituted by two phosphoryl groups, one being bound to position 4' of the nonreducing glucosamine residue (GlcN 11) and one being a-linked [7] to the glycosidic hydroxyl group of the reducing glucosaminyl group (GlcN I) (Fig.

Flow cytometric analysis of crayfish haemocytes activated by lipopolysaccharides

“…Taken together, these results imply that crayfish haemocytes are able to react differentially to the polysaccharide and lipid A moieties of LPS, where lipid A is cytotoxic and the polysaccharide portion stimulatory. This result agrees with the recognized endotoxic properties of lipid A in LPS [29,30], and the observed reduction of toxicity of deacylated LPS that still possesses potent inflammatory properties in humans [31,32]. The reaction of live haemocytes to LPS Rc, and LPSdex is similar to the reported effects of these molecules on the proPO activation from cell lysates, where LPS Rc was effective in activating the system and LPSdex was not [12].…”

Inhibition of Lipopolysaccharide Activity by a Bacterial Cyclic Lipopeptide Surfactin

“…Most of the pathological activities of LPS are attributed to its lipid A portion, which consists of a backbone of 2 phosphorylated glucosamine molecules acylated with fatty acids [1,2].…”

Comparison of lipids A of several Salmonella and Escherichia strains by 252Cf plasma desorption mass spectrometry

“…have been most extensively studied (20,22). They constitute the favorite material for investigation of endotoxin activities (10,19,31). Since the lipid portion (lipid A) of endotoxic lipopolysaccharide (LPS) has been shown to be responsible for most of the biological activities of these macromolecules, it is the focal point of such studies.…”