PD-1 induced-alveolar macrophages M1 polarization contributes to lung ischemia-reperfusion injury via SHP1/2-PI3K/Akt signaling

Abstract

Background: Lung ischemia-reperfusion injury (LIRI) is a common and complex pathophysiological process. Activation of alveolar macrophages (AMs) is involved in the inflammatory response and tissue damage during LIRI. Programmed cell death factor-1 (PD-1) plays an important role in immunomodulatory participants in diseases progression by regulating apoptosis and polarization of macrophages. In this study, we investigated the function of PD-1 on macrophage polarization during pulmonary ischemia-reperfusion.Methods: We conducted experiments both in a rat model of lung ischemia/reperfusion injury and in NR8383 cells (a rat alveolar macrophage line) model of oxygen-glucose deprivation-reoxygenation (OGD/R). The extent of lung injury was measured by pathohistological lung tissue damage, wet/dry ratios of pulmonary tissue, levels of inflammatory factors. Western blot was used to detect the relative expression of PD-1, SHP1, SHP2, p-Akt, and Akt. Expression of surface markers on macrophages was measured by immunohistochemistry, flow cytometry, and immunofluorescence staining.Results: The results showed that the expression of PD-1 increased in both in vivo and in vitro models, which promoted the polarization of M1 macrophages, resulting in the aggravation of the pulmonary ischemia-reperfusion injury. These effects were at least partially attributable to PD-1 inhibiting the PI3K/Akt pathway by regulating SHP1/2. Conclusion: PD-1 may exacerbate LIRI by promoting macrophage polarization, and inhibition of PD-1 may be an important role and therapeutic target of acute lung injury.