A Brief Review of the Role of Macrophage Hypoxia in SiO₂‐Induced Pulmonary Fibrosis

Silicosis, a severe occupational chronic pneumonia, results from prolonged exposure to high concentrations of crystalline SiO2 in occupational environments. The inhaled SiO2 particles recruit and activate alveolar macrophages (AMs), leading to hypoxia within the AMs that causes a series of biological changes in AMs. These changes include morphological alterations, inflammatory responses, cell death, and secretion of fibrosis-associated cytokines, inducing silicosis fibrosis. Unfortunately, no systematic elaboration exists in this area. In this review, we first summarize the relevant literature that describes the relationship between AM hypoxia and silicosis, and the complex and multifaceted mechanisms by which SiO2 particles lead to hypoxia in AMs. Then, we introduce a series of cascading reactions triggered by AM hypoxia. These reactions gradually result in the differentiation of the target downstream cells, fibroblasts, and alveolar epithelial Type II cells into myofibroblasts, causing the development of pulmonary fibrosis. Lastly, we introduce the current clinical treatments for pulmonary fibrosis targeting AM hypoxia. This review may not only help us deeply understand the role of hypoxia but also offer a potential therapeutic strategy for the prevention and treatment of SiO2-induced pulmonary fibrosis.