Immunological Responses in a Murine Model Following Inhalation Exposure to Be Metal, BeO, and AlBe

Abstract

RationaleChronic beryllium disease (CBD) is a progressive granulomatous lung disease and characterized by mononuclear cell infiltration and granulomatous inflammation in the lung. Affected individuals have a Be-specific hypersensitivity response involving CD4+ T-lymphocytes and production of Th1 type cytokines.MethodsC3H/HeJ mice were exposed to Be metal, BeO, and AlBe, total and respirable particles. Beryllium lymphocyte proliferation test (BeLPT) was used to explore the presence of Be-specific immune responses in spleen. Cytokine assays were performed in bronchoalveolar lavage. Flow cytometry analysis was conducted to determine expression of T cell and intracellular IFN-γ. Standard histology of lung was used to explore cellular infiltration and granulomatous inflammation.ResultsExposure to Be compounds led to marked pulmonary inflammation. The expression of CD4+, CD8+, and IFN-γ stained with florescence labelled antibodies indicated a significantly greater expression among Be metal, BeO, and AlBe exposed mice, particularly respirable particles. Proliferation response as Stimulation Index was significantly higher for Be exposed mice than control. Cytokine assays of bronchoalveolar lavage revealed significant increased level of Th1 type cytokines including IL-2, TNF-α, and IFN-γ for mice exposed to Be compounds compared to control, predominantly respirable particles.ConclusionsCytokines production, expression of CD4+, and lung inflammation are in correlation with the immunological effects being seen in human with CBD. Our findings suggest that respirable particles may induce more pronounced immunological effects than total. This study provide a novel model as a basis for further study to investigate the importance role of particle size for identify a scientifically based threshold to protect workers against CBD. RationaleChronic beryllium disease (CBD) is a progressive granulomatous lung disease and characterized by mononuclear cell infiltration and granulomatous inflammation in the lung. Affected individuals have a Be-specific hypersensitivity response involving CD4+ T-lymphocytes and production of Th1 type cytokines. Chronic beryllium disease (CBD) is a progressive granulomatous lung disease and characterized by mononuclear cell infiltration and granulomatous inflammation in the lung. Affected individuals have a Be-specific hypersensitivity response involving CD4+ T-lymphocytes and production of Th1 type cytokines. MethodsC3H/HeJ mice were exposed to Be metal, BeO, and AlBe, total and respirable particles. Beryllium lymphocyte proliferation test (BeLPT) was used to explore the presence of Be-specific immune responses in spleen. Cytokine assays were performed in bronchoalveolar lavage. Flow cytometry analysis was conducted to determine expression of T cell and intracellular IFN-γ. Standard histology of lung was used to explore cellular infiltration and granulomatous inflammation. C3H/HeJ mice were exposed to Be metal, BeO, and AlBe, total and respirable particles. Beryllium lymphocyte proliferation test (BeLPT) was used to explore the presence of Be-specific immune responses in spleen. Cytokine assays were performed in bronchoalveolar lavage. Flow cytometry analysis was conducted to determine expression of T cell and intracellular IFN-γ. Standard histology of lung was used to explore cellular infiltration and granulomatous inflammation. ResultsExposure to Be compounds led to marked pulmonary inflammation. The expression of CD4+, CD8+, and IFN-γ stained with florescence labelled antibodies indicated a significantly greater expression among Be metal, BeO, and AlBe exposed mice, particularly respirable particles. Proliferation response as Stimulation Index was significantly higher for Be exposed mice than control. Cytokine assays of bronchoalveolar lavage revealed significant increased level of Th1 type cytokines including IL-2, TNF-α, and IFN-γ for mice exposed to Be compounds compared to control, predominantly respirable particles. Exposure to Be compounds led to marked pulmonary inflammation. The expression of CD4+, CD8+, and IFN-γ stained with florescence labelled antibodies indicated a significantly greater expression among Be metal, BeO, and AlBe exposed mice, particularly respirable particles. Proliferation response as Stimulation Index was significantly higher for Be exposed mice than control. Cytokine assays of bronchoalveolar lavage revealed significant increased level of Th1 type cytokines including IL-2, TNF-α, and IFN-γ for mice exposed to Be compounds compared to control, predominantly respirable particles. ConclusionsCytokines production, expression of CD4+, and lung inflammation are in correlation with the immunological effects being seen in human with CBD. Our findings suggest that respirable particles may induce more pronounced immunological effects than total. This study provide a novel model as a basis for further study to investigate the importance role of particle size for identify a scientifically based threshold to protect workers against CBD. Cytokines production, expression of CD4+, and lung inflammation are in correlation with the immunological effects being seen in human with CBD. Our findings suggest that respirable particles may induce more pronounced immunological effects than total. This study provide a novel model as a basis for further study to investigate the importance role of particle size for identify a scientifically based threshold to protect workers against CBD.