Annexin A1 (AnxA1) is an endogenous
protein that modulates anti-inflammatory processes, and its therapeutic potential has been reported in a range of inflammatory diseases. The effect of AnxA1 on
ischemia-reperfusion (IR)-induced
lung injury has not been examined. In this study, isolated, perfused rat lungs were subjected to IR
lung injury induced by
ischemia for 40 min, followed by reperfusion for 60 min. The rat lungs were randomly treated with vehicle (
phosphate-buffered saline), and Ac2-26 (an active N-terminal
peptide of AnxA1) with or without an N-
formyl peptide receptor (FPR) antagonist N-
Boc-Phe-Leu-Phe-Leu-Phe (Boc2). An in vitro study of the effects of Ac2-26 on human alveolar epithelial cells subjected to
hypoxia-reoxygenation was also investigated. Administration of Ac2-26 in IR
lung injury produced a significant attenuation of lung
edema, pro-inflammatory
cytokine production recovered in bronchoalveolar lavage fluid, oxidative stress, apoptosis, neutrophil infiltration, and lung tissue injury. Ac2-26 also decreased AnxA1
protein expression, inhibited the activation of nuclear factor-κB and
mitogen-activated protein kinase pathways in the injured lung tissue. Finally, treatment with Boc2 abolished the protective action of Ac2-26. The results indicated that Ac2-26 had a protective effect against
acute lung injury induced by IR, which may be via the activation of the FPR.