Ultrastructural and biochemical changes in alveolar macrophages exposed to nickel hydroxy carbonate.
The aim of this investigation was to assess the cytotoxic effect of nickel hydroxy carbonate (NiHC) on guinea pig alveolar macrophages (AMs) by studying ultrastructural modifications and by determining beta-glucuronidase (BG) and lactate dehydrogenase (LDH) activities, as well as cellular ATP content. The ultrastructural studies revealed phagocytosis of NiHC particles and a general vacuolisation of the cells, especially at high concentrations. X-ray microprobe analyses of these particles demonstrated the presence of Ni, P and Ca which suggests the formation of Ni-P-Ca complexes. In exposed cells, a biphasic change in intracellular ATP concentrations was observed which could indicate 'activation' of AMs at low concentrations and inhibition of energy generation at higher concentrations. As for enzymatic activities, a dose-dependent increase in LDH release was observed except at low doses which increased ATP. There was a good correlation between ATP decrease and LDH release, consistent with a dose-dependent cytotoxic effect of NiHC. However beta-glucuronidase activity remained unchanged at all NiHC concentrations. It has been concluded that NiHC undergoes an intracellular, biological transformation to form Ni-P-Ca. Further investigations are needed to determine the precise nature and importance of these complexes.
Laboratoire de Pathologie Respiratoire Expérimentale et de Pollution Atmosphérique, Institut Pasteur, Lille, France.
K
K
Arsalane
H F
HF
Hildebrand
R
R
Martinez
B
B
Wallaert
C
C
Voisin
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D006168:Guinea Pigs; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D008854:Microscopy, Electron; D009532:Nickel / Q000494:pharmacology*
D009532:Nickel; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; C030989:nickel carbonate