A role for cell adhesion in beryllium-mediated lung disease.
Chronic beryllium disease (CBD) is a debilitating lung disorder in which exposure to the lightweight metal beryllium (Be) causes the accumulation of beryllium-specific CD4+ T cells in the lung and formation of noncaseating pulmonary granulomas. Treatment for CBD patients who exhibit progressive pulmonary decline is limited to systemic corticosteroids, which suppress the severe host inflammatory response. Studies in the past several years have begun to highlight cell-cell adhesion interactions in the development of Be hypersensitivity and CBD. In particular, the high binding affinity between intercellular adhesion molecule 1 (I-CAM1) on lung epithelial cells and the beta(2) integrin LFA-1 on migrating lymphocytes and macrophages regulates the concerted rolling of immune cells to sites of inflammation in the lung. In this review, we discuss the evidence that implicates cell adhesion processes in onset of Be disease and the potential of cell adhesion as an intervention point for development of novel therapies.
Hong-Geller
Elizabeth
E
Los Alamos National Laboratory, Biosciences Division, Los Alamos, New Mexico 87545, USA.
D001607:Berylliosis / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000502:physiology; D002448:Cell Adhesion; D002465:Cell Movement; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D018448:Models, Immunological; D015854:Up-Regulation
D018925:Chemokines; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1