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Gut ischemia/reperfusion activates lung macrophages for tumor necrosis factor and hydrogen peroxide production
A L Souza1, R S Poggetti, B Fontes
1Surgical Emergency Department, Hospital das Clinicas-University of São Paulo School of Medicine, Brazil.
Background:
Gut ischemia followed by reperfusion (I/R) is implicated as a prime initiating event in the mechanism of multiple organ failure after trauma and hemorrhagic shock. Several lines of evidence indicate that macrophages are involved in this prime event. Our purpose was to evaluate hydrogen peroxide (H2O2) and tumor necrosis factor (TNF) production and phagocytosis by lung macrophages in a gut I/R model of multiple organ failure in rats.
Methods:
In the experimental group (I/R), Wistar rats (n = 35) were anesthetized and subjected to a median laparotomy, and the superior mesenteric artery was clamped for 45 minutes followed by 60 minutes of reperfusion. In the control group (LAP) (n = 37), animals underwent sham laparotomy. After the period of reperfusion, bronchoalveolar lavage (BAL) was performed and the resulting BAL cells were assayed for H2O2 production using the horseradish peroxidase-mediated red phenol oxidation method. TNF release was determined using the L929 cells bioassay. Zymosan phagocytosis by BAL macrophages was quantitated using phase microscopy.
Results:
H2O2 release in BAL cells of I/R rats (19.90 +/- 7.98 nmol/L/2 x 10(5) cells) is statistically higher than in the LAP group (10.92 +/- 5.01 nmol/L per 2 x 10(5) cells) (p = 0.0155), and the TNF production by BAL cells of the I/R group (38.09 +/- 20.79 units per 10(6) cells) was significantly higher than that of LAP rats (17.16 +/- 13.35 units per 10(6) cells) (p = 0.0281). Phagocytic activity of BAL mac. Macrophages of I/R rats was not statistically different from LAP animals.
Conclusion:
These results suggest that BAL macrophage play a role in the mechanism of acute lung injury after trauma and hemorrhagic shock.
Insights
Gut ischemia reperfusion increases hydrogen peroxide and TNF production by lung macrophages, suggesting their role in acute lung injury following trauma and shock.
Area of Science:
- Physiology
- Immunology
- Pathology
Background:
- Gut ischemia-reperfusion (I/R) is a key factor in multiple organ failure after trauma and hemorrhagic shock.
- Macrophages are implicated in the initial inflammatory events of gut I/R.
- Understanding macrophage function is crucial for addressing post-traumatic organ damage.
Purpose of the Study:
- To investigate hydrogen peroxide (H2O2) and tumor necrosis factor (TNF) production by lung macrophages.
- To assess the phagocytic activity of lung macrophages in a rat model of gut I/R.
- To elucidate the role of lung macrophages in acute lung injury secondary to gut I/R.
Main Methods:
- Wistar rats underwent superior mesenteric artery clamping (45 min) followed by reperfusion (60 min) to induce gut I/R.
- Control rats underwent sham laparotomy.
- Bronchoalveolar lavage (BAL) cells were analyzed for H2O2 production, TNF release, and macrophage phagocytosis.
Main Results:
- BAL cells from I/R rats showed significantly higher H2O2 release compared to controls (p=0.0155).
- TNF production by BAL cells was significantly elevated in the I/R group versus the control group (p=0.0281).
- No significant difference in phagocytic activity was observed between I/R and control rat macrophages.
Conclusions:
- Lung macrophages exhibit increased H2O2 and TNF production following gut I/R.
- These findings suggest a role for BAL macrophages in the pathogenesis of acute lung injury.
- The study highlights macrophage-derived inflammatory mediators in multi-organ failure after shock.