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Excess iron promotes emergence of foamy macrophages that overexpress ferritin in the lungs of silicosis patients.

  • Academic Journal
  • Aloe, Christian Anthony1 (AUTHOR)
    Leong, Tracy Li‐Tsein2,3,4 (AUTHOR)
    Wimaleswaran, Hari2,3,5 (AUTHOR)
    Papagianis, Paris Clarice1 (AUTHOR)
    McQualter, Jonathan Luke1 (AUTHOR)
    McDonald, Christine Faye2,3 (AUTHOR)
    Khor, Yet Hong2,3,6 (AUTHOR)
    Hoy, Ryan Francis7,8 (AUTHOR)
    Ingle, Aviraj9 (AUTHOR)
    Bansal, Vipul9 (AUTHOR)
    Goh, Nicole Soo Leng2,3 (AUTHOR)
    Bozinovski, Steven1 (AUTHOR)
  • Respirology. Jun2022, Vol. 27 Issue 6, p427-436. 10p.
  • Background and objective: Inhalation of high concentrations of respirable crystalline silica (RCS) can lead to silicosis. RCS contains varying levels of iron, which can cause oxidative stress and stimulate ferritin production. This study evaluated iron‐related and inflammatory markers in control and silicosis patients. Methods: A cohort of stone benchtop industry workers (n = 18) were radiologically classified by disease severity into simple or complicated silicosis. Peripheral blood and bronchoalveolar lavage (BAL) were collected to measure iron, ferritin, C‐reactive protein, serum amyloid A and serum silicon levels. Ferritin subunit expression in BAL and transbronchial biopsies was analysed by reverse transcription quantitative PCR. Lipid accumulation in BAL macrophages was assessed by Oil Red O staining. Results: Serum iron levels were significantly elevated in patients with silicosis, with a strong positive association with serum ferritin levels. In contrast, markers of systemic inflammation were not increased in silicosis patients. Serum silicon levels were significantly elevated in complicated disease. BAL macrophages from silicosis patients were morphologically consistent with lipid‐laden foamy macrophages. Ferritin light chain (FTL) mRNA expression in BAL macrophages was also significantly elevated in simple silicosis patients and correlated with systemic ferritin. Conclusion: Our findings suggest that elevated iron levels during the early phases of silicosis increase FTL expression in BAL macrophages, which drives elevated BAL and serum ferritin levels. Excess iron and ferritin were also associated with the emergence of a foamy BAL macrophage phenotype. Ferritin may represent an early disease marker for silicosis, where increased levels are independent of inflammation and may contribute to fibrotic lung remodelling. Silicosis is an aggressive and incurable lung disease. In this study, serum iron levels were increased in silicosis patients, and these levels were strongly associated with serum ferritin levels. Lipid‐laden bronchoalveolar lavage macrophages were identified as a major source of ferritin, whereas markers of inflammation were not increased. See relatedEditorial [ABSTRACT FROM AUTHOR]
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