title: Immunological responses in C3H/HeJ mice following nose-only inhalation exposure to different sizes of beryllium metal particles.
abstract: Beryllium is used in a wide variety of industries. Chronic beryllium disease is the most common occupational disease among workers following exposure to Be. The objective of this study was to determine the immunologic effects of two different particle sizes of Be metal, <2.5 microm (fine Be or Be-F) and <10 microm (inhalable Be or Be-I) on C3H/HeJ mice following 3 weeks of nose-only inhalation exposure at a target concentration of 250 microg m(-3). Mice were sacrificed either on day 28 or day 42 (Be-F group only) after exposure. The mass median aerodynamic diameter obtained in the inhalation chamber was 1.5 +/- 0.1 microm for Be-F and 4.1 +/- 0.6 microm for Be-I. Results showed peri-bronchial inflammation with early granulomatous changes in exposed mice. The extent of the inflammation appeared more severe for mice sacrificed at day 42. Splenocyte proliferation was higher for mice exposed to fine particles compared with Be-I and control animals. Flow-cytometric analysis indicated a significantly greater expression of CD4(+), CD8(+) and intracellular IFN-gamma expression for both Be particle sizes, particularly for fine particles. Cytokine assays of bronchoalveolar lavage revealed significantly greater levels of IL-12, TNF-alpha and IFN-gamma for mice exposed to fine particles. Our findings suggest that exposure to fine particles may induce more pronounced immunological effects than inhalable particles.
authors.affiliation: Meakins-Christie Laboratories, McGill University, C.P. 6128 Succursale Centre-Ville, Montréal, Québec, Canada H3C 3J7.
authors.forename: Fariba
authors.initials: F
authors.lastname: Salehi
authors.forename: Joseph
authors.initials: J
authors.lastname: Zayed
authors.forename: Séverine
authors.initials: S
authors.lastname: Audusseau
authors.forename: Caroline
authors.initials: C
authors.lastname: Muller
authors.forename: Ginette
authors.initials: G
authors.lastname: Truchon
authors.forename: Philippe
authors.initials: P
authors.lastname: Plamondon
authors.forename: Gilles
authors.initials: G
authors.lastname: L'espérance
authors.forename: Gaston
authors.initials: G
authors.lastname: Chevalier
authors.forename: Bruce
authors.initials: B
authors.lastname: Mazer
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001608:Beryllium / Q000633:toxicity*; D001991:Bronchitis / Q000139:chemically induced* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006099:Granuloma / Q000139:chemically induced* / Q000473:pathology; D019570:Inhalation Exposure; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010316:Particle Size; D013154:Spleen / Q000187:drug effects* / Q000473:pathology
chemical_list: D016207:Cytokines; D001608:Beryllium