RT Journal Article
SR Electronic
T1 Lysosomal iron in pulmonary alveolar proteinosis: a case report
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 673
OP 679
DO 10.1183/09031936.00044108
VO 33
IS 3
A1 H. L. Persson
A1 L. K. Vainikka
YR 2009
UL http://erj.ersjournals.com/content/33/3/673.abstract
AB Pulmonary alveolar proteinosis is characterised by accumulation of surfactant-like material in the distal air spaces. Since lysosomes play a crucial role for degradation of large biomolecules taken up from the cell's environment, it was hypothesised that oxidant-induced lysosomal disruption and ensuing cell death might play a role in disease development. In the present study, alveolar macrophages, harvested by whole-lung lavage from a patient diagnosed with pulmonary alveolar proteinosis, are shown to contain large amounts of undigested material within lysosomes, and the same organelle exhibits increased amounts of haemosiderin-bound iron. Compared with murine macrophage-like J774 cells (iron exposed or not), the status of human macrophages was pro-oxidative, i.e. macrophages exhibited a low level of the antioxidant glutathione and large amounts of iron available for Fenton-type chemistry. As a consequence, macrophageal lysosomes were particularly fragile when exposed to physiological concentrations of hydrogen peroxide (generated by glucose oxidase in culture medium). Such lysosomal disruption resulted in extensive cell death by both necrosis and apoptosis independent of caspase-3 activation. Considering the potential role of iron-catalysed oxidant-induced lysosomal rupture and ensuing cell killing for pulmonary alveolar proteinosis pathology and disease progression, whole-lung lavage might be considered early in those cases in which cytochemical staining reveals great numbers of haemosiderin-laden alveolar macrophages.