B. Garner et al., ON THE CYTOPROTECTIVE ROLE OF FERRITIN IN MACROPHAGES AND ITS ABILITYTO ENHANCE LYSOSOMAL STABILITY, Free radical research, 27(5), 1997, pp. 487-500
Macrophages have a great capacity to take up (e.g. by endocytosis and
phagocytosis) exogenous sources of iron which could potentially become
cytotoxic, particularly following the intralysosomal formation of low
-molecular weight, redox active iron, and under conditions of oxidativ
e stress. Following autophagocytosis of endogenous ferritin/apoferriti
n, these compounds may serve as chelators of such lysosomal iron and c
ounteract the occurrence of iron-mediated intralysosomal oxidative rea
ctions. Such redox-reactions have been shown to lead to destabilisatio
n of lysosomal membranes and result in leakage of damaging lysosomal c
ontents to the cytosol. In this study we have shown: (i) human monocyt
e-derived macrophages to accumulate ferritin in response to iron expos
ure; (ii) iron to destabilise macrophage secondary lysosomes when the
cells are exposed to H2O2; and (iii) endocytosed apoferritin to act as
a stabiliser of the acidic vacuolar compartment of iron-loaded macrop
hages. While the endogenous ferritin accumulation which was induced by
iron exposure was not sufficient to protect cells from the damaging e
ffects of H2O2, exogenously added apoferritin, as well as the potent i
ron chelator desferrioxamine, afforded significant protection. It is s
uggested that intralysosomal formation of haemosiderin, from partially
degraded ferritin, is a protective strategy to suppress intralysosoma
l iron-catalysed redox reactions. However, under conditions of severe
macrophage lysosomal iron-overload, induction of ferritin synthesis is
not enough to completely prevent the enhanced cytotoxic effects of H2
O2.