Macrophage Polarization: An Important Candidate Regulator for Lung Diseases

Abstract

Macrophages are crucial components of the immune system and play a critical role in the initial defense against pathogens. They are highly heterogeneous and plastic and can be polarized into classically activated macrophages (M1) or selectively activated macrophages (M2) in response to local microenvironments. Macrophage polarization involves the regulation of multiple signaling pathways and transcription factors. Here, we focused on the origin of macrophages, the phenotype and polarization of macrophages, as well as the signaling pathways associated with macrophage polarization. We also highlighted the role of macrophage polarization in lung diseases. We intend to enhance the understanding of the functions and immunomodulatory features of macrophages. Based on our review, we believe that targeting macrophage phenotypes is a viable and promising strategy for treating lung diseases.

Advancing biomedical applications of polyoxometalate-based metal–organic frameworks: from design to therapeutic potential

“…Macrophages are widely present in vertebrates involved in non-specific defence (innate immunity) and specific defence (cellular immunity). 120 Their main functions are phagocytosis (i.e., phagocytosis as well as digestion) of cellular debris and pathogens in the form of fixed or free cells and activation of lymphocytes or other immune cells to respond to pathogens. Some drug delivery can be targeted through macrophages.…”

Extracellular vesicles as carriers for noncoding RNA-based regulation of macrophage/microglia polarization: an emerging candidate regulator for lung and traumatic brain injuries

“…However, the revelation of localized macrophages in tissue in various bodily systems, stemming throughout the growth phase of the embryo, from the yolk sac, has fundamentally altered researchers' perspectives on the origin of macrophages (18,19). Macrophages can originate either by differentiating from monocytes in circulation that come from bone marrow stem cells or by deriving from primitive macrophages that originate from the maternal liver and yolk sac of the embryo (20). Based on their lung location, macrophages can be categorized into two types: alveolar macrophages, situated on the alveolar interior surface and directly exposed to the external surroundings, having a vital part in the initial immune response; and interstitial macrophages, commonly related to airways, nerves, and vessels (21,22).…”

“…M1 macrophages engage in antimicrobial properties, generate inflammatory-promoting factors, and mediate organ injury, while M2 macrophages generate factors that reduce inflammation and facilitate organ recovery (23). M1 macrophages, frequently described as "classically activated" (proinflammatory) macrophages," become activated through stimuli like colonystimulating factor for granulocyte-macrophage colonies and TLR ligands like LPS and Th1-type cytokines (20). M1 macrophages secrete an abundance of factors that promote inflammation, including TNF-a, IL-6, IL-1b, IL-12, IL-23, CXCL1-3, CXCL-5, and CXCL8-10 (24).…”

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“…Recent efforts have focused on repurposing drugs for inflammatory lung injury and infections to switch the proinflammatory state of AMs to an antiinflammatory, pro-resolution phenotype, or to increase macrophage host defense, as reviewed in ref. 178 . Zanubrutinib targets Bruton’s tyrosine kinase (BTK) activation, inhibiting JAK2/STAT1 and TLR4/MyD88/NF-κB signaling pathways and promoting activation of STAT6 and PI3K/Akt signaling pathways ( 179 ).…”