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Paralysis of phagocyte migration due to an artificial blood substitute
TA Lane and GE Lamkin
We investigated the effect of a candidate artificial blood substitute,
Fluosol-DA (FDA), on human neutrophil function in a serum-free medium. In a
50% (vol/vol) mixture with polymorphonuclear cells (PMN), FDA had no effect
on PMN viability, phagocytosis, superoxide anion generation, degranulation,
or bactericidal activity. In striking contrast, the random migration and
chemotaxis of PMN to both f-Met-Leu-Phe (fMLP) and activated serum were
inhibited by 98% +/- 2%, 95% +/- 2%, and 88% +/- 6%, respectively.
Inhibition of chemotaxis by FDA required no preincubation, was
dose-dependent (50% inhibition [ID50] with a 14% vol/vol mixture with FDA),
and was fully reversible by washing PMN free of FDA after one hour but not
after 18 hours of incubation (32% +/- 11% inhibition of chemotaxis). FDA
itself was not chemotactic and did not impair either the chemotactic
activity or binding of fMLP to PMN. FDA also inhibited PMN adhesion (ID50,
9 +/- 1 vol/vol%). The inhibitory component of FDA was found to be its
detergent additive, Pluronic F-68, which inhibited random migration,
chemotaxis, and adhesion with ID50s of 1.4, 2.4, and 2.9 mg/mL,
respectively (equivalent to FDA concentrations of 5, 9, and 11 vol/vol%,
respectively). All the other components of FDA were noninhibitory. Plasma
samples from humans injected with 8 mL/kg FDA and plasma samples from
rabbits injected with 16 mL/kg FDA or an equivalent concentration of
Pluronic F-68, when mixed with autologous PMN, also severely inhibited PMN
chemotaxis. We conclude that exposure of PMN to clinically relevant
concentrations of FDA inhibits PMN migration, presumably due to inhibition
of adhesion. The inhibitory effect is entirely due to the detergent,
Pluronic F-68. Artificial blood substitutes containing Pluronic F-68 may
compromise the ability of PMN to prevent or effectively control microbial
infections.
Volume 64,
Issue 2,
pp. 400-405,
08/01/1984
Copyright © 1984 by The American Society of Hematology
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