Intrapulmonary administration of bone-marrow derived M1/M2 macrophages to enhance the resolution of LPS-induced lung inflammation: noninvasive monitoring using free-breathing MR and CT imaging protocols

摘要

Background Alveolar macrophages, with their high functional plasticity, were reported to orchestrate the induction and resolution of inflammatory processes in chronic pulmonary diseases. Noninvasive imaging modalities that offer simultaneous monitoring of inflammation progression and tracking of macrophages subpopulations involved in the inflammatory cascade, can provide an ideal and specific diagnostic tool to visualize the action mechanism in its initial stages. Therefore, the purpose of the current study was to evaluate the role of M1 and M2 macrophages in the resolution of lipopolysaccharide (LPS)-induced lung inflammation and monitor this process using noninvasive free-breathing MRI and CT protocols. Methods Bone-marrow derived macrophages were first polarized to M1 and M2 macrophages and then labeled with superparamagnetic iron oxide nanoparticles. BALB/c mice with lung inflammation received an intrapulmonary instillation of these ex vivo polarized M1 or M2 macrophages. The biodistribution of macrophages subpopulations and the subsequent resolution of lung inflammation were noninvasively monitored using MRI and micro-CT. Confirmatory immunohistochemistry analyses were performed on lung tissue sections using specific macrophage markers. Results As expected, large inflammatory areas noninvasively imaged using pulmonary MR and micro-CT were observed within the lungs following LPS challenge. Subsequent intrapulmonary administration of M1 and M2 macrophages resulted in a significant decrease in inflammation starting from 72?h. Confirmatory immunohistochemistry analyses established a progression of lung inflammation with LPS and its subsequent reduction with both macrophages subsets. An enhanced resolution of inflammation was observed with M2 macrophages compared to M1. Conclusions The current study demonstrated that ex vivo polarized macrophages decreased LPS-induced lung inflammation. Noninvasive free-breathing MR and CT imaging protocols enabled efficient monitoring of progression and resolution of lung inflammation.