Posttreatment with aspirin-triggered lipoxin A4 analog attenuates lipopolysaccharide-induced acute lung injury in mice: the role of heme oxygenase-1

Anesth Analg. 2007 Feb;104(2):369-77. doi: 10.1213/01.ane.0000252414.00363.c4.


Background: We hypothesized that posttreatment with 15-epi-16-parafluoro-phenoxy lipoxin A4 (ATL) could attenuate lipopolysaccharide (LPS)-induced acute lung injury in mice.

Methods: All the animals were randomly assigned to one of six groups (n = 6 per group). In the sham-vehicle group, mice were treated with 0.9% saline 60 min after they were challenged with saline. The sham-ATL group was identical to the sham-vehicle group except that ATL (0.7 mg/kg, IV) was administered, and the sham-ZnPP group was identical to the sham-vehicle group except that Zinc protoporphyrin IX (ZnPP, 25 mg/kg IV) was administered. In the LPS-vehicle group, mice were treated with vehicle 60 min after they were challenged with LPS. The LPS-ATL group was identical to the LPS-vehicle group but received ATL. The ZnPP-ATL-LPS group was identical to the LPS-ATL group, but ZnPP was administered 30 min before ATL.

Results: Inhalation of LPS increased inflammatory cell counts, tumor necrosis factor-alpha, and protein concentration in bronchoalveolar lavage fluid and also induced lung histological injury and edema. Posttreatment with ATL inhibited tumor necrosis factor-alpha, nitric oxide, and malondialdehyde production, with the outcome of decreased pulmonary edema, lipid peroxidation, and the infiltration of neutrophils in lung tissues. In addition, ATL promoted the formation of heme oxygenase-1 in the lung tissues. Heme oxygenase-1 activity was also increased in the lung tissues after ATL stimulation. The beneficial effects of ATL were abolished by ZnPP.

Conclusions: This study demonstrates that posttreatment with ATL significantly reduces LPS-induced acute lung injury in mice.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Aspirin / pharmacology
  • Aspirin / therapeutic use*
  • Heme Oxygenase-1 / antagonists & inhibitors
  • Heme Oxygenase-1 / physiology*
  • Lipopolysaccharides / toxicity*
  • Lipoxins / pharmacology
  • Lipoxins / therapeutic use*
  • Lung Diseases / chemically induced
  • Lung Diseases / enzymology*
  • Lung Diseases / pathology
  • Lung Diseases / prevention & control
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Random Allocation
  • Time Factors


  • Anti-Inflammatory Agents, Non-Steroidal
  • Lipopolysaccharides
  • Lipoxins
  • lipoxin A4
  • Heme Oxygenase-1
  • Aspirin