Macrophages: Their role, activation and polarization in pulmonary diseases

Abstract

Macrophages, circulating in the blood or concatenated into different organs and tissues constitute the first barrier against any disease. They are foremost controllers of both innate and acquired immunity, healthy tissue homeostasis, vasculogenesis and congenital metabolism. Two hallmarks of macrophages are diversity and plasticity due to which they acquire a wobbling array of phenotypes. These phenotypes are appropriately synchronized responses to a variety of different stimuli from either the tissue microenvironment or - microbes or their products. Based on the phenotype, macrophages are classified into classically activated/(M1) and alternatively activated/(M2) which are further sub-categorized into M2a, M2b, M2c and M2d based upon gene expression profiles. Macrophage phenotype metamorphosis is the regulating factor in initiation, progression, and termination of numerous inflammatory diseases. Several transcriptional factors and other factors controlling gene expression such as miRNAs contribute to the transformation of macrophages at different points in different diseases. Understanding the mechanisms of macrophage polarization and modulation of their phenotypes to adjust to the micro environmental conditions might provide us a great prospective for designing novel therapeutic strategy. In view of the above, this review summarises the activation of macrophages, the factors intricated in activation along with benefaction of macrophage polarization in response to microbial infections, pulmonary toxicity, lung injury and other inflammatory diseases such as chronic obstructive pulmonary dysplasia (COPD), bronchopulmonary dysplasia (BPD), asthma and sepsis, along with the existing efforts to develop therapies targeting this facet of macrophage biology.

NF-κB-Induced MicroRNA-211 Inhibits Interleukin-10 in Macrophages of Rats with Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome

“…Next, we focused on macrophages due to its well-acknowledged roles in acute inflammatory response [15]. As shown in Fig.…”

“…Total cells, macrophages, neutrophils and lymphocytes were remarkably enriched in the BALF from ARDS model rats, which consolidated the acute and intensive inflammatory response in LPS-stimulated animals. The macrophages are important mediator in both acute and chronic inflammation [15], here we selected this population of immune cells for further investigations. As miRNAs have been reported to serve as novel therapeutic targets in acute lung injury and ARDS [13], we adopted the strategy of miRNA microarray to interrogate the expression profile in ARDS-related inflammatory setting.…”

M2b macrophage polarization and its roles in diseases

“…M2b cells express not only high levels of IL‐10, but also low levels of IL‐12 . High IL‐10 or/and low IL‐12/IL‐10 ratio is/are widely accepted as the characteristic marker(s) of M2b macrophages . IL‐10 can be tested by quantitative real time polymerase chain reaction (Q‐PCR) for mRNA or by Western blotting, ELISA, or flow cytometry assays for protein.…”

“…M1 macrophages, which are typically induced by TLR ligands (bacterial LPS) or by some cytokines, such as IFN‐γ, TNF‐α, and GM‐CSF, are characterized by a high capacity to present antigen, high proinflammatory cytokine production (IL‐1β, IL‐6, IL‐12, and IL‐23), high chemokine (C‐X‐C motif) ligand 9 (CXCL9) production, and low levels of IL‐10 . Functionally, M1 macrophages can facilitate immunity to remove foreign pathogens and tumor cells, mediate tissue damage induced by ROS, and impair wound healing and tissue regeneration …”

TLRs in pulmonary diseases

“…Thus, TLR4 is unique as it uses both pathways [3]. Activated TLRs initiate a cascade of events which involves variety of protein kinases that eventually leads to the activation of certain transcription factors like NF-κβ, MAPKs, IRFs, AP1 [4,12]. These factors enter the nucleus, binds DNA, transcribe and translate proteins that consequently enhance innate immune response and initiate adaptive immune responses against the pathogen (Fig.…”