Heme oxygenase-1 protects against neutrophil-mediated intestinal damage by down-regulation of neutrophil p47 phox and p67 phox activity and O 2 - production in a two-hit model of alcohol intoxication and burn injury

Xiaoling Li, Martin G Schwacha, Irshad H. Chaudry, Mashkoor A. Choudhry

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47 Citations (Scopus)

Abstract

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 (∼250 g) were gavaged with EtOH to achieve a blood EtOH level of ∼100 mg/dL before burn or sham injury (∼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 1 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 neutrophil O 2 - production and protect the intestine from damage following EtOH and burn injury.

Original languageEnglish (US)
Pages (from-to)6933-6940
Number of pages8
JournalJournal of Immunology
Volume180
Issue number10
StatePublished - 2008
Externally publishedYes

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Alcoholic Intoxication
Heme Oxygenase-1
Neutrophils
Down-Regulation
Wounds and Injuries
Caspase 3
Antioxidants
neutrophil cytosol factor 67K
4-ethoxymethylene-2-phenyl-2-oxazoline-5-one
Body Surface Area
Superoxides
Intestines
Chlorides
Permeability
Edema
Body Weight
Apoptosis

ASJC Scopus subject areas

  • Immunology

Cite this

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title = "Heme oxygenase-1 protects against neutrophil-mediated intestinal damage by down-regulation of neutrophil p47 phox and p67 phox activity and O 2 - production in a two-hit model of alcohol intoxication and burn injury",
abstract = "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 (∼250 g) were gavaged with EtOH to achieve a blood EtOH level of ∼100 mg/dL before burn or sham injury (∼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 1 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 neutrophil O 2 - production and protect the intestine from damage following EtOH and burn injury.",
author = "Xiaoling Li and Schwacha, {Martin G} and Chaudry, {Irshad H.} and Choudhry, {Mashkoor A.}",
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T1 - Heme oxygenase-1 protects against neutrophil-mediated intestinal damage by down-regulation of neutrophil p47 phox and p67 phox activity and O 2 - production in a two-hit model of alcohol intoxication and burn injury

AU - Li, Xiaoling

AU - Schwacha, Martin G

AU - Chaudry, Irshad H.

AU - Choudhry, Mashkoor A.

PY - 2008

Y1 - 2008

N2 - 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 (∼250 g) were gavaged with EtOH to achieve a blood EtOH level of ∼100 mg/dL before burn or sham injury (∼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 1 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 neutrophil O 2 - production and protect the intestine from damage following EtOH and burn injury.

AB - 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 (∼250 g) were gavaged with EtOH to achieve a blood EtOH level of ∼100 mg/dL before burn or sham injury (∼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 1 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 neutrophil O 2 - production and protect the intestine from damage following EtOH and burn injury.

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