Open AccessPhysicochemical characteristics of triacyl lipid A partial structure OM‐174 in relation to biological activity
Author(s) -
Brandenburg Klaus,
Lindner Buko,
Schromm Andra,
Koch Michel H. J.,
Bauer Jacques,
Merkli Alain,
Zbaeren Claude,
Davies J. Gwynfor,
Seydel Ulrich
Publication year - 2000
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1046/j.1432-1327.2000.01370.x
Subject(s) - chemistry , lipid a , phospholipid , membrane fluidity , membrane , limulus , biological activity , biophysics , limulus amebocyte lysate , lysis , molecule , lipopolysaccharide , stereochemistry , biochemistry , organic chemistry , in vitro , biology , paleontology , endocrinology
The triacylated lipid A partial structure OM‐174 was characterized in detail using a variety of physical and biological techniques. OM‐174 aggregates adopt the micellar H I structure. The temperature ( T c ) of the gel to liquid‐crystalline phase transition of the hydrocarbon chains is 0 °C, from which high fluidity of the acyl chains at 37 °C can be deduced. The molecular area of a single OM‐174 molecule at a surface pressure of 30 mN·m −1 is 0.78 ± 0.04 nm 2 . Conformational analyses, using IR spectroscopy, of the behavior of the various functional groups of OM‐174 as compared with hexa‐acyl lipid A suggest altered hydration of the phosphate charges and unusually strong hydration of the ester groups, which is probably related to the high accessibility of these groups to water in the micellar aggregate structure. OM‐174 was shown to intercalate into a phospholipid membrane corresponding to the macrophage membrane within seconds in the presence, and within minutes to hours in the absence, of LPS‐binding protein. In the Limulus amebocyte lysate assay, the triacyl lipid A is more than 10 5 ‐fold less active than hexa‐acyl lipid A, but only 10‐fold less active in inducing IL‐6 in human mononuclear cells, and equally active in inducing NO production in murine macrophages. These findings are used to explain the mechanism of the lipid A‐induced cell activation.