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TA Lane and GE Lamkin
We previously showed that an artificial blood substitute containing
perfluorocarbons, Fluosol-DA, inhibited both neutrophil migration and
adherence, due to its detergent component, Pluronic F-68. The purpose of
the studies we report here was to determine if Fluosol or Pluronic might
also reduce in vivo neutrophil migration and impair host resistance to
bacterial infection. We studied in vivo PMN migration by injecting mice
intraperitoneally (IP) with glycogen, followed by intravenous (IV) infusion
of saline, Fluosol, or Pluronic. Peritoneal lavage after eight hours showed
a significant decrease in the accumulation of PMN in lavage fluids of
animals given either Fluosol or Pluronic (control--.19 +/- .03 X 10(6)
PMN/mL, glycogen--1.35 +/- .14; glycogen/Fluosol--0.63 +/- .12;
glycogen/Pluronic--0.69 +/- .07). We ascertained the effect of Fluosol and
Pluronic on infection mortality by injecting mice IV with saline, Fluosol,
or Pluronic, followed by a quantity of E coli (0.6 X 10(7] IP shown in
preliminary studies to kill 20% to 50% of the mice in 24 hours. The 24-hour
mortality was 14/45- saline, 24/32-Fluosol (chi 2 = 17.1; P less than .001)
and 17/23 - Pluronic (chi = 11.2; P less than .001). Neither Fluosol nor
Pluronic caused mortality without E coli. The increase in infection
mortality occurred when Fluosol was given either two hours before, or
simultaneously with E coli, but only with the simultaneous administration
of bacteria and Pluronic. Pluronic did not alter reticuloendothelial system
(RES) clearance function. These studies indicate that, in an animal model,
Fluosol-DA, due to its detergent component Pluronic F-68, impaired
neutrophil delivery to an inflammatory locus, and resulted in an increased
rate of infection mortality. Since Pluronic did not result in RES blockade,
but did impair the delivery of PMN to an inflammatory locus, our results
suggest that the latter effect is responsible for the increase in infection
mortality.
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| Copyright © 1986 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||