Beryllium induces apoptosis in human lung macrophages.
The link between metal-induced apoptosis and granulomatous inflammation in human disease pathogenesis is not established. The presence of TUNEL positive nuclei in chronic beryllium disease (CBD) pulmonary granulomas suggested the possibility that beryllium (Be) could induce apoptosis in adherent macrophages from CBD bronchoalveolar (BAL) cells. Apoptosis was measured in un-stimulated and Be-stimulated BAL adherent macrophages from CBD (n = 21) and Be-sensitized (BeS, n = 16) subjects. Be-stimulated CBD and BeS macrophages underwent caspase-dependent nuclear fragmentation, cytoplasmic membrane blebbing and CD14 loss. Be-stimulated adherent macrophage apoptosis was not due to TNF-alpha production. Apoptosis, CD14 loss and TNF-alpha production were not observed in unstimulated BAL macrophages. Thus, Be-stimulated BAL adherent macrophage apoptosis occurred whether cells were derived from patients with granulomatous inflammation or not, was caspase-mediated and occurred independent of TNF-alpha levels. We conclude that Be-induced human lung adherent macrophage apoptosis could contribute to the host's continued re-exposure to Be resulting in chronic granulomatous inflammation.
Kittle
Lori A
LA
Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206, USA.
Sawyer
Richard T
RT
Fadok
Valerie A
VA
Maier
Lisa A
LA
Newman
Lee S
LS
D017209:Apoptosis / Q000187:drug effects*; D001607:Berylliosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D001608:Beryllium / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008213:Lymphocyte Activation; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018950:Lipopolysaccharide Receptors; D014409:Tumor Necrosis Factor-alpha; D001608:Beryllium