Physicochemical characteristics of triacyl lipidâA partial structure OMâ174 in relation to biological activity
2000
Brandenburg, Klaus | Lindner, Buko | Schromm, Andra | Koch, Michel H. J. | Bauer, Jacques | Merkli, Alain | Zbaeren, Claude | Davies, J Gwynfor | Seydel, Ulrich
The triacylated lipidâA partial structure OMâ174 was characterized in detail using a variety of physical and biological techniques. OMâ174 aggregates adopt the micellar HI structure. The temperature (Tc) of the gel to liquidâcrystalline phase transition of the hydrocarbon chains is 0â°C, from which high fluidity of the acyl chains at 37â°C can be deduced. The molecular area of a single OMâ174 molecule at a surface pressure of 30âmN·m−1 is 0.78â±â0.04ânm2. Conformational analyses, using IR spectroscopy, of the behavior of the various functional groups of OMâ174 as compared with hexaâacyl lipidâA 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. OMâ174 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 LPSâbinding protein. In the Limulus amebocyte lysate assay, the triacyl lipidâA is more than 105âfold less active than hexaâacyl lipidâA, but only 10âfold less active in inducing ILâ6 in human mononuclear cells, and equally active in inducing NO production in murine macrophages. These findings are used to explain the mechanism of the lipidâAâinduced cell activation.
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