Annexin-A1 peptide down-regulates the leukocyte recruitment and up-regulates interleukin-10 release into lung after intestinal ischemia-reperfusion in mice

Abstract

BackgroundIntestinal ischemia/reperfusion (IR) injury is a serious and triggering event in the development of remote organ dysfunction, from which the lung is the main target. This condition is characterized by intense neutrophil recruitment, increased microvascular permeability. Intestinal IR is also responsible for induction of adult respiratory distress syndrome, the most serious and life-threatening form of acute lung injury. The purpose of this study was to investigate the effect of annexin-A1 protein as an endogenous regulator of the organ remote injury induced by intestinal ischemia/reperfusion. Male C57bl/6 mice were subjected to intestinal ischemia, induced by 45 min occlusion of the superior mesenteric artery, followed by reperfusion.ResultsThe intestinal ischemia/reperfusion evoked a high intensity lung inflammation as indicated by the number of neutrophils as compared to control group. Treatment with annexin-A1 peptidomimetic Ac2-26, reduced the number of neutrophils in the lung tissue and increased its number in the blood vessels, which suggests a regulatory effect of the peptide Ac2-26 in the neutrophil migration. Moreover, the peptide Ac2-26 treatment was associated with higher levels of plasma IL-10.ConclusionOur data suggest that the annexin-A1 peptidomimetic Ac2-26 treatment has a regulatory and protective effect in the intestinal ischemia/reperfusion by attenuation of the leukocyte migration to the lung and induction of the anti-inflammatory cytokine IL-10 release into the plasma. The anti-inflammatory action of annexin-A1 and its peptidomimetic described here may serve as a basis for future therapeutic approach in mitigating inflammatory processes due to intestinal ischemia/reperfusion.

Interleukin‐10 plays a key role in the modulation of neutrophils recruitment and lung inflammation during infection by Streptococcus pneumoniae

“…35 Consistently, it has been recently described that intraperitoneal administration of an Annexin-A1 peptide in an intestinal ischaemia/reperfusion injury experiment reduced migration of neutrophils into the lungs, which is associated with increased IL-10 and decreased TNF-a in plasma. 36 These data are consistent with our findings, and support the importance of IL-10 production for the protection of lung tissue after S. pneumoniae infection, probably by controlling the recruitment of neutrophils to the airways. However, further research would be required to precisely define the capacity of the IL-10 produced after S. pneumoniae infection to modulate the recruitment of neutrophils into lungs.…”

Mimetic peptide AC2-26 of annexin A1 as a potential therapeutic agent to treat COPD

“…pressure, ventilation and lung dimensions were similar to those found in control animals, showing the beneficial effects of the treatment against the systemic damages of smoking exposure. These data are in agreement with studies that demonstrate the protective role of Ac2-26 in pulmonary diseases such as lung inflammation, fibrosis and silicosis [28][29][30][31].…”

“…The low concentration of this cytokine in animals exposed to smoke without treatment indicates that this mediator is affected by exposure to cigarette smoke [60]. The administration of the AnxA1 mimetic peptide in a model of intestinal ischemia-reperfusion was beneficial, with attenuation of leukocyte migration to the lung and induction of IL-10 release into the blood [28,30]. Similar to our results, the protective effect of Ac2-26 was shown in a model of pulmonary endotoxemia by LPS administration [29], in which the pre-treatment with the peptide regulated the endotoxemic inflammation by decreasing the leukocyte extravasation to the connective tissue and alveolar cavity, reducing the release of TNF-α, IL-6 and IL-1β and increasing the IL-10 in BAL and blood plasma.…”

“…The anti-inflammatory efficacy of Ac2-26 the AnxA1 mimetic peptide (Ac-AMVSEFLKQAWFIENEEQEYVQTVK, Thermo Fisher Scientific, Grand Island, NY, USA) in protecting against inflammatory processes caused by exposure to tobacco smoke was evaluated in one of the smoke-exposed groups (n = 10) by the intraperitoneal (ip) administration of Ac2-26 at the dosage of 1 mg/kg in 100 μL of phosphate buffered (PBS) solution [28][29][30][31][32][33], once a day and before the first exposure to cigarette smoke. The treatment protocol started along with the protocol of exposure to cigarette smoke and had the same duration of 5 weeks.…”

“…After discovering that the biological activity of AnxA1 could be reproduced by the first amino acids of the N-terminal portion of the protein (peptide Ac2-26), it became common practice to use these molecules in experimental models of inflammation [27][28][29][30][31]. Intravital microscopy analysis of inflamed vessels in vivo pointed the site of action of AnxA1 in adherent leukocytes and the administration of exogenous AnxA1 or its derived peptide, Ac2-26, reduced adhesion and migration of leukocytes in the endothelium of post-capillary venules [26].…”