Characteristics and potential role of M2 macrophages in COPD

Abstract

BackgroundCOPD is a multi-pathogenesis disease mainly caused by smoking. A further understanding of the mechanism of smoking-related COPD might contribute to preventions and treatments of this disease in the early stages. This study was designed to identify the characteristics of M2 macrophages in COPD for a better understanding about their potential role.Materials and methodsCOPD models were built in the C57BL/6 mouse by cigarette smoke (CS) exposure combined with intraperitoneal injection of cigarette smoke extract (CSE). The modeling efficiency was evaluated by lung function and hematoxylin and eosin (H&E) staining. The number of different macrophage phenotypes was detected by immunohistochemical staining (IHS) of CD206, CD86 and CD68 on the lung tissue paraffin section. The RAW264.7 cells were polarized toward the M2 phenotype by interleukin IL-4 and confirmed by a flow cytometer. The gene expression levels of TGF-βRII, Smad2, Smad3 and Smad7 in CSE-treated M2 macrophages were detected by real-time reverse transcription polymerase chain reaction (RT-PCR). The expression levels of TGF-β/Smad pathway-related makers (TGF-βRII, p-Smad2, p-Smad3, Smad7 and TGF-β) in alveolar M2 macrophages were detected by two consecutive paraffin section IHS.ResultsThe COPD model is well established, which is confirmed by the lung function test and lung H&E staining. The whole number of macrophages and the ratio of M2/M1 phenotype are both increased (p<0.05). The level of CD206+ cells in IL-4-stimulated RAW264.7 cells is up to 93.4%, which is confirmed by a flow cytometer. The gene expression of TGF-βRII, Smad2, Smad3 and Smad7 are all enhanced (p<0.05) in CES-treated M2 macrophages, which is detected by RT-PCR. The protein levels of TGF-β/Smad pathway-related markers are all increased in alveolar M2 macrophages of the model group.ConclusionThis study found an increased deposition of alveolar M2 macrophages in the mouse COPD model and an increased expression level of TGF-β/Smad pathway in M2 macrophages, both in vitro and in vivo, induced by CSE and/or CS exposure, indicating that M2 macrophages might contribute to COPD through changing of phenotype and TGF-β/Smad pathway.

Pathobiological mechanisms underlying metabolic syndrome (MetS) in chronic obstructive pulmonary disease (COPD): clinical significance and therapeutic strategies

“…However, AM isolated from smokers exhibit a coordinated down-regulation of a considerable number of genes typical for M1 polarization, with a concomitant induction of a panel of genes that are typical of the M2 phenotype (Shaykhiev et al, 2009), suggesting cigarette smoke may induce reprogramming of AM toward M1-deactivated, and M2-polarized. In line with this, experimental evidence in a rodent COPD model found increased deposition of M2 AM (He, Xie, Lu, & Sun, 2017). Intriguingly, a recent study also observed attenuated glycolytic reserve and spare respiratory capacity in AM from smokers leading to impairment of glycolytic response to infection (Gleeson et al, 2018).…”

A Novel Murine Chronic Obstructive Pulmonary Disease Model and the Pathogenic Role of MicroRNA-21

“…These other diseases share one point in common—a massive infiltration of immunocytes in the inflammation tissue. In the same manner, our group previously found that macrophages, mainly the M2 phenotype, tend to deposit in the alveoli of COPD mice, which could be related to TGF-β/Smad pathway (He et al, 2017 ); this pathway was concerned to be a target of miR-21 (Davis et al, 2008 ). To confirm that the rise of miR-21 is not only local but also circulatory, our group analyzed the miRs expression profile in COPD by microarray and confirmed by RT-qPCR that miR-21 is ascendant in the serum of COPD patients and asymptomatic heavy smokers (Xie et al, 2014 ).…”

Tobacco Smoke Induces and Alters Immune Responses in the Lung Triggering Inflammation, Allergy, Asthma and Other Lung Diseases: A Mechanistic Review

“…M2 macrophages are involved in the encapsulation and destruction of parasites, immunoregulation, matrix deposition and tissue remodeling. It has been shown that the exposure to cigarette smoke induces a unique macrophage polarization pattern marked by a suppression of M1 and an induction of M2-related genes signatures [ 175 , 176 , 177 ]. The impact of cigarette smoke on macrophage polarization is multifaceted and not limited to changes in the lung cytokine milieu.…”