Dual polarization of human alveolar macrophages progressively increases with smoking and COPD severity

Erica Bazzan,Marco Schiavon,Federico Rea,Graziella Turato,Marina Saetta,Simonetta Baraldo,Mariaenrica Tinè,Elisabetta Balestro,Claudia M Radu,Paolo Simioni,Fiorella Calabrese,Manuel G Cosio,Francesca Lunardi,Chiara Rigobello,Davide Biondini

doi:10.1186/s12931-017-0522-0

Erica Bazzan, Marco Schiavon + Show 13 more

Open Access

https://doi.org/10.1186/s12931-017-0522-0

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Abstract

BackgroundIt is known that tissue macrophages derive not only from blood monocytes but also from yolk sac or fetal liver, and the tissue of residence guides their function. When isolated, they lose tissue specific signatures, hence studies of human macrophages should be ideally done directly in the tissue. The aim of this study was to investigate directly in human lung tissue the polarization of alveolar macrophage (AM), classic (M1) or alternative (M2), in health and disease, using COPD as a model.MethodsSurgical lungs from 53 subjects were studied: 36 smokers whose FEV1 varied from normal to severe COPD, 11 non-smokers and 6 normal donors. iNOS and CD206 immunohistochemistry was used to quantify the percentage of AM polarized as M1 or M2 in lung sections.Results and DiscussionThe percentage of M1 and M2 increased progressively with smoking and COPD severity, from 26% to 84% for M1 and from 7% to 78% for M2. In donors 74% of AM were negative for M1 and 93% for M2. Confocal microscopy showed co-localization of M1 and M2 in the same AM in severe COPD.ConclusionIn normal lungs alveolar macrophages were mostly non-polarized. With smoking and COPD severity, M1 and M2 polarization increased significantly and so did the co-expression of M1 and M2 in the same alveolar macrophage.

Highlights

It is known that tissue macrophages derive from blood monocytes and from yolk sac or fetal liver, and the tissue of residence guides their function
It is evident that macrophages, which are present in almost all tissues, coordinate immunological, metabolic and developmental functions contributing to the maintenance of homeostasis
It is clear that the M1/M2 classification might be simplistic [6, 7] since a spectrum of macrophage phenotypes has been observed in in vitro experiments [5], the M1/M2 nomenclature [8] is still

Summary

Introduction

It is known that tissue macrophages derive from blood monocytes and from yolk sac or fetal liver, and the tissue of residence guides their function. When isolated, they lose tissue specific signatures, studies of human macrophages should be ideally done directly in the tissue. Upon encountering pathogens or danger signals, macrophages express a strong pro-inflammatory profile including cytokines and reactive oxygen and nitrogen species. This pro-inflammatory phenotype is recognized as the “classically activated” or M1 phenotype and can be produced in vitro in response to inflammatory stimuli like Lipopolysaccharides (LPS) or Interferon (IFN)-γ [3,4,5]. It is clear that the M1/M2 classification might be simplistic [6, 7] since a spectrum of macrophage phenotypes has been observed in in vitro experiments [5], the M1/M2 nomenclature [8] is still

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