Bioscience Division, B

Elizabeth Hong-Geller Invited to Write Review of Chronic Beryllium Disease

Chronic Beryllium Disease (CBD) is a debilitating lung disorder in which exposure to beryllium causes the accumulation of beryllium-specific CD4+ T cells in the lung and formation of pulmonary granulomas. Elizabeth Hong-Geller (B-7) was invited to write a review, “A Role for Cell Adhesion In Beryllium-Mediated Lung Disease” for a special edition on physiological effects of beryllium in the Journal of Occupational and Environmental Hygiene. The U.S. Occupational Safety and Health Administration (OSHA) has instituted a defined exposure limit to protect workers from beryllium overexposure. Nevertheless, cases of CBD, including in the DOE complex, continue to occur. This underscores the need for fundamental research to understand the molecular mechanisms of beryllium disease. Treatment for CBD patients who exhibit progressive pulmonary decline is limited to systemic corticosteroids, which suppress the host’s inflammatory response.

Studies in the last several years have begun to highlight cell-cell adhesion interactions in the development of beryllium 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 movement of immune cells to sites of inflammation in the lung. In the review, Hong-Geller discusses the evidence that implicates cell adhesion processes in the onset of CBD and the potential of cell adhesion as an intervention point for development of novel therapies. Blocking LFA-1 function can inhibit T cell proliferation and cytokine release, two signal activation pathways in CBD. This finding suggests that anti-LFA-1 antibodies, in addition to anti-I-CAM1 antibodies, may be potential candidates for intervention in CBD. Inhibition of LFA-1/I-CAM1 interactions may prevent the leukocyte adhesion and migration process that occurs during the immune response to beryllium in the lung, and ultimately reduce the chronic inflammation associated with CBD. Past LDRD-DR funding for the project “Beryllium Specific Immune Response and Development Of Chronic Beryllium Disease” supported the work.

>>>More Highlights

B-7 Teams

• Environmental Assessment
• Forensics
• Host & Pathogen Biology
• Security Analysis & Applications
• Signature Design and Computation

Focus on Research

Links / Resources

• National Institutes of Health