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Review
. 2023 Mar 4;28(5):2379.
doi: 10.3390/molecules28052379.

Macrophage Polarization: An Important Candidate Regulator for Lung Diseases

Lishuang Deng  1 , Zhijie Jian  1 , Tong Xu  1 , Fengqin Li  2 , Huidan Deng  1 , Yuancheng Zhou  3 , Siyuan Lai  1 , Zhiwen Xu  1   4 , Ling Zhu  1   4
Affiliations
Review

Macrophage Polarization: An Important Candidate Regulator for Lung Diseases

Lishuang Deng et al. Molecules. .

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.

Keywords: M1/M2; lung disease; macrophage; polarization; signaling pathway.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
The origin and tissue distribution of macrophages. Primitive macrophages are derived from the yolk sac and fetal liver and circulating monocytes are derived from bone marrow. Macrophages are widely distributed in tissues and organs of the body, including blood, skin, brain, heart, lung, liver, spleen, and kidney.
Figure 2
Figure 2
Schematic diagram of macrophage subtypes. Under stimulation by GM-CSF, IFN-γ, and LPS, M0 macrophages polarize into M1 macrophages. Alternatively, M-CSF, IL-4, IL-13, and IC stimulation lead to polarization of M0 macrophages into M2 macrophages. Various cytokines further induce M2 macrophages to differentiate into M2a, M2b, M2c, and M2d phenotypes. M1, M2a, M2b, M2c and M2d macrophages express distinct biomarkers and secrete diverse cytokines. Green letters represent cytokines or factors that promote macrophage polarization. Orange letters represent biomarkers of macrophages. Blue letters indicate cytokines secreted by macrophages.
Figure 3
Figure 3
Signaling pathways associated with macrophage polarization. There are five primary signaling pathways: PI3K/AKT signaling pathway, TLRs/NF-κB signaling pathway, JAK-STAT signaling pathway, Notch signaling pathway, and JNK signaling pathway. These pathways modulate macrophage polarization individually or in conjunction with others. Negative regulation between adjacent molecules is indicated by red lines, while positive regulation is represented by arrows. Molecules that promote macrophage polarization toward the M1 phenotype are depicted by blue arrows, and those that promote M2 polarization are shown by pink arrows.
Figure 4
Figure 4
Schematic diagram of important lung diseases involving macrophage polarization. Macrophage polarization plays a crucial role in the pathophysiology of various lung diseases, including acute lung injury, chronic obstructive pulmonary disease, asthma, tuberculosis, and lung cancer.
See this image and copyright information in PMC

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