Transcriptional and functional diversity of human macrophage repolarization

Abstract

Background: Macrophage plasticity allows cells to adopt different phenotypes, a property with important implications in disorders such as cystic fibrosis (CF) and asthma. Objective: We sought to examine the transcriptional and functional significance of macrophage repolarization from an M1 to an M2 phenotype and assess the role of a common human genetic disorder (CF) and a prototypical allergic disease (asthma) in this transformation. Methods: Monocyte-derived macrophages were collected from healthy subjects and patients with CF and polarized to an M2 state by using IL-4, IL-10, glucocorticoids, apoptotic PMNs, or azithromycin. We performed transcriptional profiling and

Macrophage polarization: Reaching across the aisle?

“…Overall, the results by Gharib et al 1 represent an important step forward in understanding the transcriptional and functional diversity of human macrophages repolarized to an M2 phenotype in response to distinct stimuli and provide a new approach to guide the interrogation of human macrophage phenotypes in the context of clinically relevant inflammatory diseases, with critical implications for the development of novel and more effective therapeutic strategies.…”

“…Macrophage polarization can influence the pathogenesis of many human diseases; however, the transcriptional program regulating this process remains poorly characterized. Gharib et al 1 highlight the high diversity of M1-to-M2 repolarization exerted by distinct M2 stimuli through transcriptome-based pathway analysis and provide a new approach to phenotype human macrophages in clinically relevant disease states, such as cystic fibrosis (CF) and asthma.…”

“…M2-polarized macrophages have been implicated in the immunopathogenesis of asthma, 4 but the transcriptional profile of alveolar macrophages after acute allergen exposure has not been explored previously. In the study by Gharib et al, 1 in vitro-derived M2 transcriptional signatures were used to fingerprint the alveolar macrophage polarization state in an established human model of acute allergen-induced asthma using gene set enrichment analysis. Results of this analysis provide the first evidence that the transcriptional program of alveolar macrophages in patients with allergic asthma is concordant with IL-4-and IL-10-induced and discordant with azithromycin-and methylprednisolone-induced hMDM expression profiles (Fig 2).…”

Toward the Characterization of Human Pro-Resolving Macrophages?

“…Another explanation is the in vitro culture step/system necessary to obtain human macrophages (22). Different cytokine cocktails influence significantly macrophage phenotypes (18,51). Again, the use of the same protocols for both mouse and human cells does not always lead to the same function (15).…”

Hybridization‐chain‐reaction is a relevant method for in situ detection of M2d‐like macrophages in a mini‐pig model

“…28 Interestingly, the most important macrophages for angiogenesis are thought to be the M2d macrophages ( Figure 1). 2,3,5,8,17,25,26 To advance our understanding of muscle regeneration in this IR-ASC model system, we undertook an analysis of macrophage polarization in vivo with a focus on the role played by M2d-like macrophages.…”