Alveolar macrophages polarization switch via α2-adrenoceptor activation ameliorates pulmonary inflammation following kidney ischemia reperfusion.

Purpose: The present study aimed to explore the anti-inflammatory mechanism of dexmedetomidine (Dex), an α₂-adrenoceptor (α₂-AR) agonist, in renal ischemia-reperfusion (RIR)-induced acute lung injury (ALI).

Methods: RIR was induced in C57BL/6J mice by bilateral renal pedicles occlusion for 60 min followed by 24 h of reperfusion. Mice were pretreated with Dex alone or in combination with atipamezole (Atip), an α₂-AR antagonist. Pulmonary histopathological assessment, arterial blood gas analysis, cell count and multiple cytokine examination in bronchoalveolar lavage fluid (BALF), evaluation of the global inflammation status in lung tissue, and investigation of alveolar macrophage phenotypes were carried out. In vitro, the polarization of mouse alveolar macrophages (MH-S) treated with serum from normal or RIR mice was indirectly detected by quantitative polymerase chain reaction (qPCR).

Results: The findings demonstrated that, in comparison to RIR animals, dexmedetomidine mitigated lung injury and remarkably promoted macrophage polarization towards an anti-inflammatory M2 phenotype in the pulmonary tissue. Concurrently, a reduction in inflammatory cell infiltration and levels of pro-inflammatory cytokines was observed. In vitro studies verified that dexmedetomidine directed MH-S towards the M2 phenotype after stimulation with RIR serum. However, these effects were mostly reversed following administration of atipamezole.

Conclusion: Dexmedetomidine alleviates renal ischemia-reperfusion-induced ALI by activating α₂-adrenoceptor, thereby inducing macrophage polarization towards an anti-inflammatory phenotype and reducing pulmonary global inflammation.