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