AUTOREGULATION OF HEPATIC MACROPHAGE ACTIVATION IN SEPSIS
| Autor: | Michael West, Melvin P. Bubrick, Robin Manthei |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
Lipopolysaccharides
medicine.medical_specialty Kupffer Cells medicine.medical_treatment Indomethacin Critical Care and Intensive Care Medicine Dinoprostone Sepsis Internal medicine medicine Homeostasis Macrophage Autoregulation Cells Cultured Dose-Response Relationship Drug business.industry Monokines Bacterial Infections Macrophage Activation medicine.disease In vitro medicine.anatomical_structure Endocrinology Liver Cell culture Protein Biosynthesis Hepatocyte lipids (amino acids peptides and proteins) Surgery Tumor necrosis factor alpha business Prostaglandin E |
| Zdroj: | Europe PubMed Central |
| ISSN: | 0022-5282 |
| DOI: | 10.1097/00005373-199304000-00001 |
| Popis: | Endotoxin (LPS)-stimulated macrophages release mediators, such as tumor necrosis factor (TNF) and prostaglandin E2 (PGE2), which modulate the function of many different cells. We hypothesize that macrophage regulation is altered in sepsis and that mediators from LPS-stimulated macrophages "autoregulate" their activation state. Alterations in the LPS dose response relationships for inhibition of hepatocyte protein synthesis by hepatic macrophages (hMøs) were examined to investigate factors that regulate hMø activation. In vitro pretreatment was compared using TNF alpha, PGE2, subactivating concentrations of LPS, or LPS plus indomethacin. Pre-exposure to LPS resulted in a dose-dependent loss of subsequent LPS-triggered activation of hMøs in co-culture. Pretreatment with LPS and 1 mumol/L indomethacin partially restored hMø responsiveness. Pre-exposure to PGE2 significantly decreased LPS responsiveness of co-cultured hMøs, suggesting that PGE2 produced by LPS-stimulated hMøs may mediate this effect. Pretreatment of hMøs with TNF alpha, but not IL-1 beta, significantly lowered the LPS concentration required for maximal hMø activation. We conclude that both macrophage mediators and LPS pretreatment alter macrophage activation state. These data suggest an "autoregulatory" role for mediators of LPS-stimulated macrophages in sepsis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|