Abstract
M. Tech.
The persistent presence of neutrophils is associated with a wide range of inflammatory
diseases. Resolution of inflammation in these diseases is also associated with the
ingestion of apoptotic neutrophils by macrophages.
Inflammation and apoptosis of inflammatory cells are common known features
observed in the lung following exposure to crystalline silica. What is not known is how
well these apoptotic cells are cleared by macrophages in the presence of crystalline
silica? To investigate the latter, we incubated the U937 macrophages and neutrophils
with crystalline silica and found that it could increase their apoptosis and necrosis
especially those of the U937 cells. We then examined the ability of crystalline silica to
induce the production of cytokines (TNF-α, IFN-γ and IL-1β) as well as NO by these
cells. We found that these particles could increase the production of TNF-α, IL-1β and
NO but not IFN-γ in a time-and concentration-dependent manner.
We also assessed the ability of crystalline silica to alter the levels of GSH in neutrophils
and U937 macrophages. We found that it could drastically decrease the levels of this
antioxidant in U937 macrophages with no additional effect in neutrophils as these latter
cells would have low levels of GSH prior to their incubation with crystalline silica.
Finally, we examined the effect of crystalline silica on the ability of U937 macrophages
to phagocytose apoptotic neutrophils. We found that while untreated U937 macrophages were able to phagocytose apoptotic neutrophils, the presence of
crystalline silica reduced this ability by 15%.
Taken together, our results suggest that exposure to crystalline silica impairs the
clearance of apoptotic neutrophils by decreasing their phagocytosis by macrophages
and thus prevents the resolution of inflammation.