Abstract
This review summarizes the structure and function of the alveolar unit, comprised of alveolar macrophage and epithelial cell types that work in tandem to respond to infection. Granulocyte-macrophage colony-stimulating factor (GM-CSF) helps to maintain the alveolar epithelium and pulmonary immune system under physiological conditions and plays a critical role in restoring homeostasis under pathologic conditions, including infection. Given the emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and global spread of coronavirus disease 2019 (COVID-19), with subsequent acute respiratory distress syndrome, understanding basic lung physiology in infectious diseases is especially warranted. This review summarizes clinical and preclinical data for GM-CSF in respiratory infections, and the rationale for sargramostim (yeast-derived recombinant human [rhu] GM-CSF) as adjunctive treatment for COVID-19 and other pulmonary infectious diseases.
Highlights
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a global health crisis emphasizes the importance of understanding the coordination and crosstalk between alveolar epithelial cells (AECs) and alveolar macrophages (AMs) in maintaining lung physiology during viral illness (Lang et al, 2020)
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is an immune-modulating cytokine that plays a critical role in maintaining the alveolar epithelium and pulmonary immune system under homeostatic and pathologic conditions, including infection (Rosler and Herold, 2016; Lang et al, 2020)
In COVID-19, instead of lung monocytes developing into AMs with sufficient GM-CSF signal, they develop into proinflammatory CD163+ hemophagocytic macrophages
Summary
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a global health crisis emphasizes the importance of understanding the coordination and crosstalk between alveolar epithelial cells (AECs) and alveolar macrophages (AMs) in maintaining lung physiology during viral illness (Lang et al, 2020). Granulocyte-macrophage colony-stimulating factor (GM-CSF) is an immune-modulating cytokine that plays a critical role in maintaining the alveolar epithelium and pulmonary immune system under homeostatic and pathologic conditions, including infection (Rosler and Herold, 2016; Lang et al, 2020). GM-CSF drives AM differentiation and homeostasis and maintains the integrity of the lung epithelium under near-constant exposure to inhaled pathogens (Trapnell and Whitsett, 2002; Rosler and Herold, 2016). In response to external insult, GM-CSF facilitates and accelerates the epithelial wound-healing process, driving the immune functions of the AMs and the repair processes initiated in the alveolar epithelium, including restoration of barrier function, and facilitating a return to homeostasis (Rosler and Herold, 2016)
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