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Changes in the production of nitric oxide and superoxide by inflammatory cells in liver cirrhosis
1Department of Preclinical and Clinical Pharmacology, University of Flourence, Italy.
Abstract:
Superoxide (O2-) and nitric oxide (NO) production by polymorphonuclear leukocyte (PMNs) and monocytes in patients with liver cirrhosis were evaluated. PMNs obtained from cirrhotic patients were less effective than those from controls in producing O2- after stimulation with opsonized zymosan, while they were more effective in producing NO, as shown by the inhibition of platelet aggregation and by the increase in cGMP content. NO synthase activity was higher in leukocytes from cirrhotic patients than in controls. A correlation was found between the cardiac index and the observed changes in the inflammatory cells.
Insights
Liver cirrhosis patients show altered inflammatory cell function. Polymorphonuclear leukocytes (PMNs) produce less superoxide but more nitric oxide (NO), indicating a shift in immune response related to liver disease.
Area of Science:
- Immunology
- Hepatology
- Cellular Biology
Background:
- Liver cirrhosis is associated with systemic inflammation and altered immune cell function.
- Polymorphonuclear leukocytes (PMNs) and monocytes play critical roles in innate immunity and inflammation.
- Understanding immune cell responses in cirrhosis is crucial for managing complications.
Purpose of the Study:
- To evaluate superoxide (O2-) and nitric oxide (NO) production by PMNs and monocytes in patients with liver cirrhosis.
- To investigate the activity of NO synthase in leukocytes from cirrhotic patients.
- To explore correlations between inflammatory cell changes and hemodynamic parameters like cardiac index.
Main Methods:
- Isolation of PMNs and monocytes from cirrhotic patients and healthy controls.
- Stimulation of leukocytes with opsonized zymosan to assess O2- production.
- Measurement of NO production through inhibition of platelet aggregation and cGMP content analysis.
- Assay of NO synthase activity in leukocyte extracts.
- Correlation analysis between cellular function and cardiac index.
Main Results:
- PMNs from cirrhotic patients exhibited reduced O2- production compared to controls.
- Leukocytes from cirrhotic patients demonstrated enhanced NO production, evidenced by platelet aggregation inhibition and increased cGMP.
- Higher NO synthase activity was observed in leukocytes of cirrhotic patients.
- A significant correlation was found between the cardiac index and alterations in inflammatory cell function.
Conclusions:
- Immune cell dysfunction, specifically reduced O2- and increased NO production by PMNs, is characteristic of liver cirrhosis.
- Elevated NO synthase activity contributes to the altered inflammatory profile in cirrhotic patients.
- These immune cell changes may be linked to hemodynamic alterations, suggesting a complex interplay in the pathophysiology of liver cirrhosis.