Abstract
Macrophages play an important role in the innate and adaptive immune responses of organ systems, including the lungs, to particles and pathogens. Cumulative results show that macrophages contribute to the development and progression of acute or chronic inflammatory responses through the secretion of inflammatory cytokines/chemokines and the activation of transcription factors in the pathogenesis of inflammatory lung diseases, such as acute lung injury (ALI), acute respiratory distress syndrome (ARDS), ARDS related to COVID-19 (coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)), allergic asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). This review summarizes the functions of macrophages and their associated underlying mechanisms in the development of ALI, ARDS, COVID-19-related ARDS, allergic asthma, COPD, and IPF and briefly introduces the acute and chronic experimental animal models. Thus, this review suggests an effective therapeutic approach that focuses on the regulation of macrophage function in the context of inflammatory lung diseases.
Highlights
Macrophages are innate immune cells that perform phagocytosis and eliminate pathogens as part of physiological processes [1]
A previous study indicated that the upregulation of Jun N-terminal kinase (JNK) expression and c-Myc transcription could promote the M2 phenotype in IL-4-stimulated macrophages [28,29]. These results indicate that nuclear factor-κB (NF-κB), suppressor of cytokine signaling 3 (SOCS3), STAT1/3, and IRF5 play an important role in the polarization of M1 macrophages and that JNK plays a dual role in M1/M2 macrophage polarization
Li et al reported that the increase in neutrophil/macrophage numbers and of IL-6 and tumor necrosis factor-α (TNF-α) in BALF and transforming growth factor-β (TGF-β) in lung tissue was confirmed in bleomycin-induced mice, and this increase could be suppressed with antioxidants by upregulating heme oxygenase-1 (HO-1) induction and nuclear factor erythroid-2-related factor 2 (Nrf2) activation [55]
Summary
Macrophages are innate immune cells that perform phagocytosis and eliminate pathogens as part of physiological processes [1]. Microbial components are recognized by resident AMs through their pattern-recognition receptors (PRRs), which, in turn, induce nuclear factor-κB (NF-κB)-dependent polarization into M1-type macrophages, leading to initiation of the exudative phase [17] In this phase, M1 macrophages have been reported to produce inflammatory cytokines, chemokines, and toxic molecules such as tumor necrosis factor-α (TNF-α), interleukin-1 β (IL-1β), IL-6, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein 2 (MIP-2), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and reactive oxygen species (ROS), which are associated with the recruitment of inflammatory cells, including monocytes and neutrophils, and the promotion of airway inflammation, antimicrobial activity, and lung tissue injury [8,18]. Li et al reported that the increase in neutrophil/macrophage numbers and of IL-6 and TNF-α in BALF and TGF-β in lung tissue was confirmed in bleomycin-induced mice, and this increase could be suppressed with antioxidants by upregulating HO-1 induction and Nrf activation [55]
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