Upregulation of I-CAM1 in response to beryllium exposure in small airway epithelial cells.
Chronic Beryllium Disease (CBD) is a delayed-type hypersensitivity immune reaction that leads to granuloma formation in the lungs and potentially severe loss of pulmonary function. Although the molecular mechanisms that mediate beryllium (Be)-stimulated granuloma formation are not well understood, cell adhesion molecules are likely to play a key role in the migration of immune cells to sites of inflammation. In this study, we examined the role of the cell adhesion molecule I-CAM1 in Be-stimulated small airway epithelial cells (SAECs). These epithelial cells line the airway and represent the first point of contact for inhaled foreign substances. We find that Be exposure specifically induced I-CAM1 expression on the cell surface of SAEC and release of soluble I-CAM1 into the extracellular medium. Furthermore, anti-I-CAM1 antibodies inhibited Be-stimulated adhesion of SAEC to the macrophage cell-line THP1, indicating that the Be-induced adhesive properties of SAEC are at least partly due to I-CAM1 expression. These studies support a model in which I-CAM1 cell adhesion functions may play a role in directing immune cells to the lung and activating a Be-specific immune response in Be hypersensitivity disease.
Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
Shannan
S
Rodriguez
Yuliya A
YA
Kunde
T Mark
TM
McCleskey
Elizabeth
E
Hong-Geller
D019138:Antibodies, Blocking / Q000494:pharmacology; D001608:Beryllium / Q000633:toxicity*; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D018928:Immunity, Mucosal / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013267:Stilbenes / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects*
D019138:Antibodies, Blocking; D012333:RNA, Messenger; D013267:Stilbenes; C020711:beryllium sulfate; D018799:Intercellular Adhesion Molecule-1; C041525:3,3',4,5'-tetrahydroxystilbene; D001608:Beryllium