Differences in antibody-dependent cellular cytotoxicity against tumor cells in in vitro differentiating mononuclear phagocytes from bone marrows of normal and inflamed mice.
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Biomedical subjects
Publications and source records attributed to U Schade.
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Bone marrow-derived macrophages were stimulated by the addition of zymosan. Phagocytic activity and prostaglandin release were taken as a measure of the activation state of the macrophages. Repeated stimulation with zymosan of macrophages which had been freed from extracellular zymosan led to further phagocytosis and prostaglandin formation. Very low amounts of prostaglandins were synthesized after the second phagocytic stimulus if the time interval between the first and second stimulation was one or two hours. In contrast, however, if the second phagocytic stimulation occurred 9 hours after the first stimulation there was a doubling of the number of phagocytosed zymosan particles and a fifteen fold increase in prostaglandin synthesis. These findings are explained as the consequences of internalized membrane material which provides additional substrates for the generation of prostaglandins.
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The chemical structure of the lipid A component of enterobacterial lipopolysaccharide (LPS) is now known in some detail. For example, lipid A of Escherichia coli consists of a beta(1----6)-linked D-glucosamine disaccharide that carries four (R)-3-hydroxytetradecanoyl groups in positions 2, 3, 2', and 3' and two phosphoryl residues in positions 1 and 4'. The hydroxy fatty acids at positions 2' and 3' are acylated at their 3-hydroxyl groups by dodecanoic acid and tetradecanoic acid, respectively. The hydroxyl groups in positions 4 and 6' are free, the latter serving as the attachment site for the polysaccharide component in intact LPS. On the basis of this structure, E. coli-type lipid A and partial structures thereof have been chemically synthesized (group of T. Shiba, Osaka University, Osaka, Japan) and analyzed for endotoxic activity. In all in vivo and in vitro test systems employed (including lethal toxicity, pyrogenicity, local Shwartzman reactivity, B lymphocyte mitogenicity, macrophage activation, and serologic cross-reactivity with lipid A antiserum), synthetic lipid A has activity identical to that of E. coli lipid A. These findings support the structural proposal for lipid A and prove the previous hypothesis that the endotoxic principle is embedded in lipid A.