Journal
JOURNAL OF IMMUNOLOGY
Volume 180, Issue 10, Pages 6933-6940Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.180.10.6933
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- NIAAA NIH HHS [R21 AA 015979-01A1, R21 AA015979-01A1, R01 AA015731-01A2, R01 AA 015731-01A2, R21 AA015979, R01 AA015731] Funding Source: Medline
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Heme oxygenase-1 (HO-1) has been demonstrated to protect against tissue injury. Furthermore, HO-1 is also shown to be antioxidant. Our recent findings indicate that acute alcohol (EtOH) intoxication exacerbates postburn intestinal and lung tissue damage, and this was found to be neutrophil dependent. Because neutrophil-mediated tissue injury involves the release of superoxide anions (O-2(-)), the present study examined the role of HO-1 in neutrophil O-2(-) production following EtOH and burn injury. Furthermore, we investigated whether HO-1 antioxidant properties are mediated via modulation of p47(phox) and/or p67(phox) proteins. Male rats (similar to 250 g) were gavaged with EtOH to achieve a blood EtOH level of similar to 100 mg/dL before burn or sham injury (similar to 12.5 % total body surface area). Some rats were treated with HO-1 activator cobalt protoporphyrin IX chloride (Copp; 25 mg/kg body weight) at the time of injury. On day I after injury, we found that EtOH combined with burn injury significantly increased neutrophil O-2(-) production and p47(phox) and p67(phox) activation and decreased caspase-3 activity and apoptosis. This was accompanied with a decrease in neutrophil HO-1 levels. The treatment of animals with HO-1 activator Copp normalized neutrophil HO-1, O-2(-), p47(phox), and p67(phox) following EtOH and burn injury. The expression of caspase-3, however, was further decreased in Copp_treated sham and EtOH plus burn groups. Moreover, Copp treatment also prevented the increase in intestinal edema and permeability following EtOH and burn injury. Altogether, these findings provide a new insight into the mechanism by which HO-1 regulates nentrophil O-2(-) production and protect the intestine from damage following EtOH and burn injury.
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