Biological activities of synthetic lipid A analogs: pyrogenicity, lethal toxicity, anticomplement activity, and induction of gelation of Limulus amoebocyte lysate
- 30 April 1984
- journal article
- research article
- Published by American Society for Microbiology in Infection and Immunity
- Vol. 44 (2), 421-426
- https://doi.org/10.1128/iai.44.2.421-426.1984
Abstract
Chemically synthesized lipid A analogs were investigated for several endotoxic activities, including pyrogenicity, lethal toxicity, anticomplement activity and the capacity to gelate Limulus amoebocyte lysate in comparison to natural [Salmonella minnesota] lipid A. The synthetic preparations contained D-glucosamine or D-glucosamine-.beta.-1,6-D-glucosamine disaccharide substituted by ester- and amide-bound hydroxylated or non-hydroxylated fatty acids and by PO43- groups in different combinations. Some preparations which were insoluble in H2O were succinylated and thus rendered more soluble. Strong biphasic pyrogenic responses with a maximal increase in body temperature of 1-2.degree. C were obtained with 50 .mu.g/kg doses of 3 disaccharide preparations of 15 tested. With 2 preparations (50 .mu.g/kg) moderate pyrogenicity with monophasic fever curves and a maximal temperature increase of .apprx. 0.6.degree. C was obtained. Lethal toxicity tests were carried out in galactosamine-sensitized mice. Of 15 synthetic preparations, 4 exhibited lethal toxicity under these conditions. The ED of the lipid A analogs in both in vivo tests were several hundred times higher than those of bacterial lipid A. For the activities in vivo, hydroxyacyl residues seemed to be important. Anticomplement activity was demonstrable in 7 preparations, 1 of which expressed an activity comparable to that of lipid A. Preparations containing non-hydroxylated fatty acids seemed to be most active in this test. None of the synthetic preparations exhibited gelation activities for Limulus amoebocyte lysate when tested in doses up to 0.4; bacterial free lipid A was active in doses of .apprx. 2 pg. None of the monosaccharide derivatives exhibited any of these activities.This publication has 14 references indexed in Scilit:
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