Chronic granulomatous pneumonia and lymphocytic responses induced by inhaled beryllium metal in A/J and C3H/HeJ mice

Journal Article · Wed Dec 31 04:00:00 EST 1997 · Toxicologic Pathology

DOI:https://doi.org/10.1177/019262339702500102· OSTI ID:602798

Nikula, K J; Swafford, D S; Hoover, M D; Tohulka, M D; Finch, G L ^[1]

---

1. Inhalation Toxicology Research Institute, Albuquerque, NM (United States)

Inhalation of beryllium (Be) has been associated with 2 syndromes: an acute chemical pneumonitis and a granulomatous lung disease known as chronic beryllium disease (CBD). The purpose of this study was to establish a mouse model of CBD using the inhalation route of exposure. A/J (H-2a haplotype) and C3H/HeJ (H-2{sup k}) Mice were exposed once for 90 min in nose-only exposure tubes to aerosols of Be metal. Six mo later, lung histopathologic responses were assessed. Further analyses defined the phenotypic profile of lymphocytes in pulmonary lesions and evaluated proliferation of lymphocytes in situ and in response to Be in vitro. Responses were similar in both strains of mice. Most Be-exposed mice had minimal to mild interstitial fibrosis. The majority of lymphocytes in interstitial infiltrates and in microgranulomas were CD4+ T cells. Interstitial compact aggregates of lymphocytes contained B cells centrally and CD4+ cells peripherally. Lymphocyte labeling indices, used to assess proliferation in situ, were significantly greater within microgranulomas compared to compact lymphocytic aggregates. Lymphocyte stimulation indices in response to BeSO{sub 4} in vitro were not positive in blood, spleen, or tracheobronchial lymph node samples. Be-specific immune responses and nonspecific inflammatory responses to toxic and foreign-body properties of Be may have contributed to the histopathology in both strains of mice. The interstitial mononuclear cell infiltrates, presence of microgranulomas, multinucleated foreign-body and Langhans giant cells, interstitial fibrosis, and CD4+ T-cell predominance with local proliferation are features similar to CBD in humans. The chronic lung disease induced in these mice by inhaled Be can be used to investigate the importance of variables such as dose, exposure pattern, and physicochemical form of Be in producing this disease. 29 refs., 6 figs., 3 tabs.

• Sponsoring Organization: USDOE
• DOE Contract Number: AC04-76EV01013
• OSTI ID: 602798
• Journal Information: Toxicologic Pathology, Journal Name: Toxicologic Pathology Journal Issue: 1 Vol. 25; ISSN 0192-6233; ISSN TOPADD
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
56 BIOLOGY AND MEDICINE
APPLIED STUDIES
AEROSOLS
BERYLLIUM
BIOLOGICAL MODELS
CELL PROLIFERATION
DOSES
FIBROSIS
GRANULOMAS
HISTOLOGY
INHALATION
LUNGS
LYMPHOCYTES
MICE
OCCUPATIONAL EXPOSURE
PATHOGENESIS
PNEUMONIA
PNEUMONITIS
RADIONUCLIDE KINETICS
RESPIRATORY SYSTEM DISEASES
RETENTION
TUMOR CELLS