Involvement of Prostaglandin E and Adenosine 3’,5’-Monophosphate in Lipopolysaccharide-Stimulated Collagenase Release by Rat Kupffer Cells

Kupffer cells exposed to bacterial lipopolysaccharide in vitro synthesized collagenase and released the major portion of it into the extracellular space while the intracellular level of enzyme was not altered significantly. Cycloheximide prevented the appearance of collagenase in the medium indicating de novo synthesis. Indomethacin, an inhibitor of cyclooxygenase, also blocked collagenase synthesis. In line with this observation, Kupffer cells were found to synthesize substantial amounts of prostaglandin E₂ when exposed to lipopolysaccharide; concomitantly, cellular cAMP levels were increased. Indomethacin was shown to abolish the stimulated cAMP formation. Addition to the culture medium of cAMP or dibutyryladenosine 3’, 5’-monophosphate as well as of prostaglandin EZ or, to a lesser extent, prostaglandin El allowed indomethacin-inhibited cells to resume the production of collagenase. It is proposed that in rat Kupffer cells lipopolysaccharide-elicited collagenase synthesis and excretion is mediated sequentially by stimulated production of prostaglandin E2, enhanced adenylate cyclase activity and increased intracellular cAMP levels

Experience report - Developing an evaluation scheme for the National Academy of Sciences of Ukraine based on experiences of the Leibniz Association

This report summarizes insights gained during the project "Eval-Science" that has been financed by the Federal Ministry of Research and Education (BMBF) and the Ukrainian Ministry of Research and Education. In this report, we discuss the new evaluation procedure that the National Academy of Sciences of Ukraine (NASU) has adopted to evaluate its research institutes. Due to similarities we propose how procedures of the Leibniz Association can provide a useful reference point to further improve the evaluations of the NASU

Influence of the supramolecular structure of free lipid A on its biological activity

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°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 37 b4, 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°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°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

Evaluating Science - a German-Ukrainian experience

This final document of the research project "Eval-Science", funded by the Federal Ministry of Research and Education (BMBF) and the Ukrainian Ministry of Research and Education, summarizes the rationale and main results