Role of Kupffer cells in gut ischemia/reperfusion-induced hepatic microvascular dysfunction in mice
| Autor: | T P Shanley, Robert E. Wolf, Y Horie, D. N. Granger, Janice Russell |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Pathology
medicine.medical_specialty Kupffer Cells Anti-Inflammatory Agents Ischemia Gadolinium Inflammation medicine.disease_cause Mice chemistry.chemical_compound Fibrinolytic Agents Internal medicine Cell Adhesion Leukocytes medicine Animals Intestinal Mucosa Hepatology Platelet-activating factor Tumor Necrosis Factor-alpha business.industry Kupffer cell Alanine Transaminase Leukostasis Azepines Triazoles medicine.disease Intestines Mice Inbred C57BL Chemotaxis Leukocyte Oxidative Stress P-Selectin medicine.anatomical_structure Endocrinology chemistry Reperfusion Injury Tumor necrosis factor alpha Endothelium Vascular medicine.symptom business NADP Platelet Aggregation Inhibitors Intravital microscopy Oxidative stress Liver Circulation |
| Zdroj: | Hepatology. 26:1499-1505 |
| ISSN: | 1527-3350 0270-9139 |
| DOI: | 10.1002/hep.510260617 |
| Popis: | Kupffer cells (KCs) have been implicated in the leukocyte recruitment and microvascular dysfunction associated with liver inflammation. The overall objective of this study was to assess the role of KCs in the leukocyte adhesion and oxidative stress elicited in the liver by gut ischemia/reperfusion (I/R). The accumulation of rhodamine-6G-labeled leukocytes and the number of nonperfused sinusoids (NPS) were monitored (by intravital microscopy) in mouse liver for 1 hour after a 15-minute period of normothermic intestinal ischemia. Autofluorescence of pyridine nucleotide [NAD(P)H] was measured as an index of mitochondrial O2 consumption and redox status. Leukostasis, as well as increases in NPS and NAD(P)H autofluorescence (indicating hypoxia), were observed in the liver at 60 minutes after gut I/R. Pretreatment with gadolinium chloride (GdCl3), which reduces KC function, attenuated the liver leukostasis and NPS elicited by gut I/R. The platelet activating factor (PAF) antagonist, WEB2086, and a tumor necrosis factor (TNF)-alpha-specific antibody were also effective in attenuating the gut I/R-induced leukostasis and NAD(P)H autofluorescence. The findings of this study suggest that KCs play an important role in mediating the leukocyte recruitment, impaired sinusoidal perfusion, and tissue hypoxia elicited in the liver after gut I/R. These KC-mediated responses appear to involve the participation of both PAF and TNF-alpha. (Hepatology 1997 Dec;26(6):1499-505) |
| Databáze: | OpenAIRE |
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