INFLUENCE OF THE SUPRAMOLECULAR STRUCTURE OF FREE LIPID-A ON ITS BIOLOGICAL-ACTIVITY

被引:139
作者
BRANDENBURG, K
MAYER, H
KOCH, MHJ
WECKESSER, J
RIETSCHEL, ET
SEYDEL, U
机构
[1] MAX PLANCK INST IMMUNBIOL,W-7800 FREIBURG,GERMANY
[2] EUROPEAN MOLEC BIOL LAB,HAMBURG,GERMANY
[3] UNIV FREIBURG,INST BIOL 2,W-7800 FREIBURG,GERMANY
来源
EUROPEAN JOURNAL OF BIOCHEMISTRY | 1993年 / 218卷 / 02期
关键词
D O I
10.1111/j.1432-1033.1993.tb18409.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The three-dimensional supramolecular structures and the states of order of the acyl chains of lipid A from different Gram-negative species were investigated at 40-degrees-C, high water content (80-90%), and different [lipid A]/[Mg2+] molar ratios using synchrotron radiation X-ray diffraction and Fourier-transform infrared spectroscopy. Measurements were made on free lipid A from Salmonella minnesota R595, mono- and bi-phosphoryl, as well as those from the non-enterobacterial strains Rhodobacter capsulatus 37b4, Rhodopseudomonas viridis F, and Rhodocyclus gelatinosus 29/1. Parallel to differences in their chemical primary structure, the structural polymorphisms and states of order at 37-degrees-C of the non-enterobacterial lipid A were found to be different from those of enterobacterial lipid A. A clear correlation between the supramolecular structure and previously determined biological activities was found. Lipid A with a strong preference for lamellar structures (Rb. capsulatus and Rp. viridis) are endotoxically inactive and lack cytokine-inducing capacity; the compounds assuming a mixed lamellar/nonlamellar structure (monophosphoryl lipid A from S. minnesota) are of lower toxicity in vivo, but may induce cytokines in vitro: those lipid A with a strong tendency to form non-lamellar inverted structures (lipid A from S. minnesota and Rc. gelatinosus) exhibit full endotoxicity in vitro and in vivo. In contrast, anti-complementary activity is most pronounced for compounds with lamellar and least expressed for those with inverted structures. The states of order at 37-degrees-C vary non-systematically, exhibiting the highest values for lipid A of S. minnesota and the lowest for that of Rc. gelatinosus. We propose to extend the term 'endotoxic conformation', which is used to describe the conformation of a single lipid A molecule required for optimal triggering of biological effects, to 'endotoxic supramolecular conformation' which denotes the particular organization of lipid A aggregates in physiological fluids causing biological activity.
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页码:555 / 563
页数:9
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