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Physiology Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02115
Because
mononuclear phagocytes take up perfluorochemical emulsions (PFCE), we
examined how prior treatment with PFCE affects the fate of circulating
bacteria. Rats were preinjected with three daily intravenous injections
of PFCE (2.0 ml/100 g) containing 12.5% (vol/vol) of a 4:1 mixture of
F-dimethyl adamantane and F-trimethylbicyclo-nonane, 2.5%
(wt/vol) Pluronic F-68 as the emulsifying agent, and 3%
(wt/vol) hydroxyethyl starch as the oncotic agent.
Pseudomonas aeruginosa or
Staphylococcus aureus were injected 4 h after the third PFCE injection. PFCE pretreatment decreased the
rate and extent of vascular clearance of P. aeruginosa, with decreased uptake by the liver.
Importantly, there were significant decreases in killing of
P. aeruginosa in the liver, lungs,
spleen, and kidneys of PFCE animals. PFCE did not alter the clearance of S. aureus from the circulation.
However, hepatic uptake was reduced, with concomitant increases in lung
and kidney uptake. Ultrastructure of Kupffer cells revealed PFCE
inclusions and extensive vacuolization. These experiments demonstrate
that the clearance kinetics and organ distribution of circulating
P. aeruginosa and their subsequent
killing are altered by PFCE. Diminished hepatic phagocyte function
leads to a decrease in vascular clearance of circulating bacteria,
increased uptake in other reticuloendothelial organs, and decreased
bactericidal activity versus P. aeruginosa.
lung injury; liver; macrophage
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