Beryllium-stimulated apoptosis in macrophage cell lines.

Abstract

In vitro stimulation of bronchoalveolar lavage cells from patients with chronic beryllium disease (CBD) induces the production of TNF-alpha. We tested the hypothesis that beryllium (Be)-stimulated TNF-alpha might induce apoptosis in mouse and human macrophage cell lines. These cell lines were selected because they produce a range of Be-stimulated TNF-alpha. The mouse macrophage cell line H36.12j produces high levels of Be-stimulated TNF-alpha. The mouse macrophage cell line P388D.1 produces low, constitutive, levels of TNF-alpha and does not up-regulate Be-stimulated TNF-alpha production. The DEOHS-1 human CBD macrophage cell line does not produce constitutive or Be-stimulated TNF-alpha. Apoptosis was determined by microscopic observation of propidium iodide stained fragmented nuclei in unstimulated and BeSO(4)-stimulated macrophage cell lines. BeSO(4) induced apoptosis in all macrophage cell lines tested. Beryllium-stimulated apoptosis was dose-responsive and maximal after 24 h of exposure to 100 microM BeSO(4). In contrast, unstimulated and Al(2)(SO(4))(3)-stimulated macrophage cell lines did not undergo apoptosis. The general caspase inhibitor BD-fmk inhibited Be-stimulated macrophage cell line apoptosis at concentrations above 50 microM. Our data show that Be-stimulated macrophage cell line apoptosis was caspase-dependent and not solely dependent on Be-stimulated TNF-alpha levels. We speculate that the release of Be-antigen from apoptotic macrophages may serve to re-introduce Be material back into the lung microenvironment, make it available for uptake by new macrophages, and thereby amplify Be-stimulated cytokine production, promoting ongoing inflammation and granuloma maintenance in CBD.

• Authors: R T Sawyer, V A Fadok, L A Kittle, L A Maier, L S Newman
• Journal: Toxicology (Toxicology) Vol. 149 Issue 2-3 Pg. 129-42 (Aug 21 2000) ISSN: 0300-483X [Print] Ireland
• PMID: 10967410 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Tumor Necrosis Factor-alpha
• Beryllium

Topics

• Animals
• Apoptosis (drug effects)
• Berylliosis (blood, etiology, pathology)
• Beryllium (adverse effects, pharmacology)
• Bronchoalveolar Lavage Fluid (cytology)
• Cell Line
• Chronic Disease
• Dose-Response Relationship, Drug
• Humans
• Lymphocyte Activation (drug effects)
• Lymphocytes (cytology, drug effects, immunology)
• Macrophages (cytology, drug effects, metabolism)
• Occupational Exposure (adverse effects)
• Phagocytes (cytology, drug effects, metabolism)
• Tumor Necrosis Factor-alpha (metabolism)