Quinine uptake by human polymorphonuclear neutrophils.

Abstract:

:The antimalarial drug quinine has been shown to impair human polymorphonuclear leukocyte (PMN) functions. To gain insight into the mechanism of this phenomenon, we investigated quinine uptake by PMN with a fluorometric assay based on the fluorescence properties of this drug. After 30 min of incubation at 37 degrees C in the presence of 1 and 10 micrograms of quinine per ml, PMN-associated quinine reached 90 +/- 6 and 780 +/- 150 ng/2.5 x 10(6) PMN, respectively, giving a cellular-to-extracellular concentration ratio of 140 to 150. A steady state was reached within 5 min. Uptake was partially dependent on temperature, cell viability, and extracellular pH. Fractionation studies showed that 30 to 40% of the PMN-associated quinine was located in the particulate fraction. The efflux of PMN-associated quinine was rapid and complete when the incubation mixture was replaced by drug-free medium. These data suggest that several mechanisms are involved in the uptake of quinine by PMN, including a viability- and energy-independent process possibly related to reversible association of quinine to cell structures (particularly the membrane). Other mechanisms could involve trapping by protonation and/or active PMN transport systems. Thus, most of the quinine taken up by resting PMN is found in the soluble fraction of disrupted cells. This may partly explain the depressive properties of quinine.

authors

el Benna J,Pasquier C,Labro MT

doi

10.1128/aac.35.7.1474

subject

Has Abstract

pub_date

1991-07-01 00:00:00

pages

1474-8

issue

7

eissn

0066-4804

issn

1098-6596

journal_volume

35

pub_type

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