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
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.