Macrophage Polarization in Acute Lung Injury

Acute lung injury (ALI) represents a life-threatening syndrome characterised by diffuse alveolar damage, pulmonary oedema and severe hypoxaemia. Central to its pathogenesis are macrophages, versatile immune cells that orchestrate both initiation and resolution of pulmonary inflammation. Upon tissue injury or infection, resident alveolar macrophages and recruited monocyte-derived macrophages undergo functional polarisation into classically activated (M1) or alternatively activated (M2) states. M1 macrophages predominate in the early phase of ALI, releasing proinflammatory mediators such as tumour necrosis factor-α and interleukin-1β, driving neutrophil recruitment and amplifying tissue damage. As the inflammatory response evolves, a switch towards the M2 phenotype promotes debris clearance, secretion of anti-inflammatory cytokines and tissue repair mechanisms. Dysregulation of this dynamic balance can exacerbate injury or impair healing, emphasising the global imperative to elucidate the molecular cues governing macrophage plasticity. Advances in understanding macrophage polarisation hold promise for innovative interventions that restore pulmonary homeostasis and mitigate the considerable morbidity and mortality associated with ALI.

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Macrophage Polarization in Acute Lung Injury publication trend

The graph below shows the total number of articles in macrophage polarization in acute lung injury across all publications each year (not limited to Nature Index journals).

Technical terms

Macrophage polarisation: The process by which macrophages adopt distinct functional programmes (M1 or M2) in response to environmental cues.

M1 macrophages: Classically activated macrophages that produce proinflammatory cytokines and reactive species, driving tissue injury.

M2 macrophages: Alternatively activated macrophages associated with anti-inflammatory actions, tissue repair and resolution of inflammation.

NF-κB signalling pathway: A key transcriptional regulator of inflammatory responses that controls expression of cytokines and adhesion molecules.

Ferroptosis: An iron-dependent form of programmed cell death characterised by lipid peroxidation and membrane damage.

Reactive oxygen species (ROS): Highly reactive molecules derived from oxygen that can mediate cellular signalling or contribute to oxidative injury.

References

1. Irf7 regulates the expression of Srg3 and ferroptosis axis aggravated sepsis-induced acute lung injury. Cellular & Molecular Biology Letters (2023).
2. HNF4A mitigates sepsis-associated lung injury by upregulating NCOA2/GR/STAB1 axis and promoting macrophage polarization towards M2 phenotype. Cell Death & Disease (2025).
3. Deleting fibroblast growth factor 2 in macrophages aggravates septic acute lung injury by increasing M1 polarization and inflammatory cytokine secretion. Molecular Biomedicine (2024).