ESCHERICHIA COLI LIPOPOLYSACCHARIDE POTENTIATION AND INHIBITION OF RAT NEONATAL MICROGLIA SUPEROXIDE ANION GENERATION
| Autor: | Alejandro M. S. Mayer, Peer B. Jacobson, Anne M. Romanic, Kyle H. Ramsey, Keith B. Glaser, Stephen Oh |
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| Rok vydání: | 1999 |
| Předmět: |
chemistry.chemical_classification
Reactive oxygen species Lipopolysaccharide Thromboxane Superoxide Biology Critical Care and Intensive Care Medicine Molecular biology Nitric oxide Thromboxane B2 chemistry.chemical_compound chemistry Biochemistry In vivo Emergency Medicine Tumor necrosis factor alpha |
| Zdroj: | Shock. 11:180-186 |
| ISSN: | 1073-2322 |
| Popis: | The effects of lipopolysaccharide (LPS) on the central nervous system, one of the first organs to be affected by sepsis, are still incompletely understood. Rat microglia (BMo) constitute the main leukocyte-dependent source of reactive oxygen species in the central nervous system. The in vitro effect of LPS on agonist-stimulated superoxide (O 2 - ) generation from BMo appears controversial. Our purpose was to determine the time- and concentration-dependent effect of Escherichia coli LPS on phorbol-12 myristate 13-acetate-stimulated O 2 - generation from BMo. Our results demonstrate that BMo O 2 - generation in vitro peaked 17 h after stimulation of with.3 ng/mL LPS. Furthermore, stimulation of BMo with LPS for 17 h resulted in the following concentration-dependent responses:.1-1 ng/mL LPS induced no prior mediator generation but potently enhanced subsequent phorbol-12 myristate 13-acetate-stimulated O 2 - generation; 3-10 ng/mL LPS caused nitric oxide, tumor necrosis factor-α (TNF-α), thromboxane B 2 and matrix metalloproteinase-9 release although partially inhibiting ensuing phorbol-12 myristate 13-acetate-stimulated O 2 - generation; 30-100 ng/mL LPS, maximized nitric oxide, TNF-α, thromboxane B 2 , matrix metalloproteinase-9 generation with concomitant lactic dehydrogenase release although strongly deactivating successive phorbol-12 myristate 13-acetate-stimulated O 2 - production. Our in vitro studies suggest that enhanced release of these four mediators (nitric oxide, TNF-α, thromboxane B 2 , and matrix metallo-proteinase-9) during stimulation of BMo with LPS might play a critical role in the subsequent ability of BMo to generate O 2 - in vivo. Potential clinical implications of our findings are suggested by the fact that LPS levels similar to the ones used in this study have been observed in cerebrospinal fluid both in Gram-negative meningitis and sepsis. |
| Databáze: | OpenAIRE |
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