Physicochemical characteristics of triacyl lipid A partial structure OM-174 in relation to biological activity

Citation
K. Brandenburg et al., Physicochemical characteristics of triacyl lipid A partial structure OM-174 in relation to biological activity, EUR J BIOCH, 267(11), 2000, pp. 3370-3377
Citations number
37
Categorie Soggetti
Biochemistry & Biophysics
Journal title
EUROPEAN JOURNAL OF BIOCHEMISTRY
ISSN journal
00142956 → ACNP
Volume
267
Issue
11
Year of publication
2000
Pages
3370 - 3377
Database
ISI
SICI code
0014-2956(200006)267:11<3370:PCOTLA>2.0.ZU;2-3
Abstract
The triacylated lipid A partial structure OM-174 was characterized in detai l 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 liqui d-crystalline phase transition of the hydrocarbon chains is 0 degrees C, fr om which high fluidity of the acyl chains at 37 degrees C can be deduced. T he molecular area of a single OM-174 molecule at a surface pressure of 30 m N.m(-1) is 0.78 +/- 0.04 nm(2). Conformational analyses, using IR spectrosc opy, 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 relat ed to the high accessibility of these groups to water in the micellar aggre gate structure. OM-174 was shown to intercalate into a phospholipid membran e 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 induci ng IL-6 in human mononuclear cells, and equally active in inducing NO produ ction in murine macrophages. These findings are used to explain the mechani sm of the lipid A-induced cell activation.