Otto H. E. Westphal (1913-2004).
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to Ernst Th Rietschel.
Explore the source record for details and available documents.
Richard Pfeiffer, working with Robert Koch in Berlin, intellectually and experimentally conceived the concept of endotoxin as a heat-stable bacterial poison responsible for the pathophysiological consequences of certain infectious diseases. Pfeiffer's definition of endotoxin included the inability to evoke neutralizing antibodies against this bacterial toxin. Alexandre Besredka, Ilya (Elie) Metchnikoff's successor at the Institut Pasteur in Paris, was the first to demonstrate that, in fact, antibodies could be engendered which were capable of suppressing the poisonous effects of endotoxin. Endotoxin and anti-endotoxin antibodies have since then fascinated researchers of many disciplines and continue to do so, particularly in the fields of diagnosis, prevention, and therapy of severe Gram-negative infections.
How does the host sense pathogens? Our present concepts grew directly from longstanding efforts to understand infectious disease: how microbes harm the host, what molecules are sensed and, ultimately, the nature of the receptors that the host uses. The discovery of the host sensors--the Toll-like receptors--was rooted in chemical, biological and genetic analyses that centred on a bacterial poison, termed endotoxin.
Explore the source record for details and available documents.
One major component of the Salmonella enterica sv. Minnesota Re deep rough mutant (strain R595) lipopolysaccharide is hepta-acyl lipid A (LA(hepta)). In a recent publication [Tanamoto K-I, Azumi S. Salmonella-type heptaacylated lipid A is inactive and acts as an antagonist of lipopolysaccharide action on human line cells. J Immunol 2000; 164: 3149-3156] the corresponding synthetic hepta-acyl lipid A (compound 516) was reported to be agonistically inactive but to rather suppress pro-inflammatory activation by the endotoxic hexa-acyl lipid A (LA(hexa), compound 506) and S-form LPS from Escherichia coli in the human macrophage-like cell lines THP-1 and U937. These results, however, were in contrast to previous findings with human mononuclear cells (hMNC) isolated from peripheral blood, in which compound 516 was found to be an agonist, expressing low, but significant, cytokine-inducing activity as compared to LA(hexa). We have investigated the structure of natural LA(hepta) from the S. enterica sv. Minnesota Re deep rough mutant strain (R595) by TLC immunoblot, MALDI-TOF mass spectrometry and NMR spectroscopy. Using these techniques, the structural identity between LA(hepta) and the synthetic compound 516 was confirmed. In corroboration of previous findings with studies employing compound 516, purified LA(hepta) was found to induce the production of TNF-alpha, IL-1beta and IL-6 in hMNC, thus displaying moderate agonistic activity. Furthermore, we showed that LA(hepta) agonistically activated nuclear translocation of NF-kappaB in THP-1 cells, thus clearly ruling out the possibility that LA(hepta) is an antagonist and that its biological activity is influenced by the type of human myeloid cells used for testing endotoxicity (hMNC versus THP-1 cells).
Explore the source record for details and available documents.