Beryllium-ferritin: lymphocyte proliferation and macrophage apoptosis in chronic beryllium disease.

Abstract

A beryllium (Be)-ferritin adduct containing 270 pm of Be stimulated proliferation of bronchoalveolar lavage (BAL) lymphocytes from subjects with chronic beryllium disease (CBD) at concentrations 5-6 logs lower than the amounts of beryllium sulfate (BeSO4) needed to induce proliferation. We observed increased apoptotic CBD BAL macrophages after exposure to both BeSO4 (50 +/- 6%, mean +/- SEM, P <0.05 versus unstimulated controls) and Be-ferritin (40 +/- 2%), whereas only 2.0 +/- 0.2% of BAL lymphocytes underwent activation-induced cell death. Be-ferritin also induced apoptosis in BAL macrophages from subjects with Be sensitization (25 +/- 3%) and in the H36.12j hybrid macrophage cell line (15 +/- 2%). Be-ferritin induced lung macrophage CD95 (Fas) expression and the activation of intracellular caspase-3, -8 and -9. Thus, lung macrophages take up Be-ferritin, delivering physiologically relevant levels of Be that promote Be antigen presentation and macrophage apoptosis. Be-ferritin thereby serves as a "Trojan Horse," triggering proliferation of Be-ferritin-specific CBD BAL T cells. We hypothesize that Be-ferritin exposure may result in persistent antigen exposure inducing Be-specific T cell clonal expansion and T cell helper type 1-type cytokine production and potentially explains the chronicity of CBD and its development years after environmental Be exposure has ceased.

• Authors: Richard T Sawyer, Brian J Day, Valerie A Fadok, Marina Chiarappa-Zucca, Lisa A Maier, Andrew P Fontenot, Lori Silveira, Lee S Newman
• Journal: American journal of respiratory cell and molecular biology (Am J Respir Cell Mol Biol) Vol. 31 Issue 4 Pg. 470-7 (Oct 2004) ISSN: 1044-1549 [Print] United States
• PMID: 15256386 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Radioisotopes
• fas Receptor
• Ferritins
• Beryllium

Topics

• Adult
• Aged
• Antigen Presentation
• Apoptosis (drug effects)
• Berylliosis (blood, etiology, pathology)
• Beryllium (adverse effects, pharmacology)
• Bronchoalveolar Lavage Fluid (cytology)
• Cell Division (drug effects)
• Cell Line
• Chronic Disease
• Dose-Response Relationship, Drug
• Female
• Ferritins (adverse effects, pharmacology)
• Humans
• Lung (cytology, immunology, metabolism)
• Lymphocyte Activation (drug effects)
• Lymphocytes (cytology, drug effects, immunology)
• Macrophages, Alveolar (cytology, drug effects, metabolism)
• Male
• Middle Aged
• Occupational Exposure (adverse effects)
• Phagocytes (cytology, drug effects, metabolism)
• Radioisotopes
• Smoking (drug therapy, immunology, metabolism)
• T-Lymphocytes (drug effects, immunology, metabolism)
• fas Receptor (metabolism)