Publikationsdatum:
1995-04-07
Beschreibung:
Shock due to Gram-negative bacterial sepsis is a consequence of acute inflammatory response to lipopolysaccharide (LPS) or endotoxin released from bacteria. LPS is a major constituent of the outer membrane of Gram-negative bacteria, and its terminal disaccharide phospholipid (lipid A) portion contains the key structural features responsible for toxic activity. Based on the proposed structure of nontoxic Rhodobacter capsulatus lipid A, a fully stabilized endotoxin antagonist E5531 has been synthesized. In vitro, E5531 demonstrated potent antagonism of LPS-mediated cellular activation in a variety of systems. In vivo, E5531 protected mice from LPS-induced lethality and, in cooperation with an antibiotic, protected mice from a lethal infection of viable Escherichia coli.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Christ, W J -- Asano, O -- Robidoux, A L -- Perez, M -- Wang, Y -- Dubuc, G R -- Gavin, W E -- Hawkins, L D -- McGuinness, P D -- Mullarkey, M A -- New York, N.Y. -- Science. 1995 Apr 7;268(5207):80-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Elsai Research Institute, Andover, MA 01810-2441, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7701344" target="_blank"〉PubMed〈/a〉
Schlagwort(e):
Animals
;
BCG Vaccine/immunology
;
Cytokines/secretion
;
Drug Design
;
Endotoxins/*antagonists & inhibitors
;
Escherichia coli Infections/immunology
;
Gram-Negative Bacteria/immunology
;
Humans
;
In Vitro Techniques
;
Lipid A/*analogs & derivatives/chemical synthesis/chemistry/pharmacology
;
Lipopolysaccharides/antagonists & inhibitors
;
Macrophages/immunology
;
Male
;
Mice
;
Mice, Inbred C57BL
;
Monocytes/immunology
;
Moxalactam/pharmacology
;
Nitric Oxide/metabolism
;
Rhodobacter capsulatus/immunology
;
Tumor Necrosis Factor-alpha/secretion
Print ISSN:
0036-8075
Digitale ISSN:
1095-9203
Thema:
Biologie
,
Chemie und Pharmazie
,
Informatik
,
Medizin
,
Allgemeine Naturwissenschaft
,
Physik
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