Abstract

BackgroundAlveolar 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.MethodsBone-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.ResultsAs 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.ConclusionsThe 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.

Highlights

  • Alveolar macrophages, with their high functional plasticity, were reported to orchestrate the induction and resolution of inflammatory processes in chronic pulmonary diseases

  • The diversity of macrophage function is not yet fully understood, it is increasingly recognized that alveolar macrophages (AM) are endowed with high functional plasticity allowing them to acquire either a classical pro-inflammatory M1 activation (M1 macrophages) or an alternatively immunoregulatory M2 activation (M2 macrophages) depending on the cross-talk of various signals they received from surrounding cells or from the pathogen itself [5, 6]

  • The average inflamed lung volume measured in the LPS group was 50.4 ± 3.7 μl and found to decrease slightly during the 1-week investigation to reach 43.8 ± 5.3 μl, whereas the average quantified value of ILV was 1.8 ± 3.9 μl in the control group (Fig. 1b)

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Summary

Introduction

With their high functional plasticity, were reported to orchestrate the induction and resolution of inflammatory processes in chronic pulmonary diseases. 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 Apart from their well-known role in phagocytosis and recognition of foreign antigens, alveolar macrophages (AM) play a key role in the induction and the resolution of inflammatory responses characteristic of lung diseases such as chronic obstructive pulmonary diseases (COPD) and acute lung inflammation (ALI) [1, 2]. Noninvasive imaging approaches, which enable simultaneous monitoring of inflammation progression and tracking of a particular cell population involved in the inflammatory cascade, can provide an ideal and specific diagnostic tool to visualize the action mechanism in its initial stages

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