In:
American Journal of Physiology-Cell Physiology, American Physiological Society, Vol. 288, No. 2 ( 2005-02), p. C396-C402
Abstract:
Pb + intoxication causes anemia that is partially due to a decreased life span of circulating erythrocytes. As shown recently, a Ca 2+ -sensitive erythrocyte scramblase is activated by osmotic shock, oxidative stress, and/or energy depletion, leading to exposure of phosphatidylserine at the erythrocyte surface. Because macrophages are equipped with phosphatidylserine receptors, they bind, engulf, and degrade phosphatidylserine-exposing cells. The present experiments were performed to explore whether Pb + ions trigger phosphatidylserine exposure of erythrocytes. The phosphatidylserine exposure was estimated on the basis of annexin binding as determined using fluorescence-activated cell sorting (FACS) analysis. Exposure to Pb + ions [≥0.1 μM Pb(NO 3 ) 2 ] significantly increased annexin binding. This effect was paralleled by erythrocyte shrinkage, which was apparent on the basis of the decrease in forward scatter in FACS analysis. The effect of Pb + ions on cell volume was virtually abolished, and the effect of Pb + ions on annexin binding was blunted after increase of extracellular K + concentration. Moreover, both effects of Pb + ions were partially prevented in the presence of clotrimazole (10 μM), an inhibitor of the Ca 2+ -sensitive K + channels in the erythrocyte cell membrane. Whole cell patch-clamp experiments disclosed a significant activation of a K + -selective conductance after Pb + ion exposure, an effect requiring higher (10 μM) concentrations, however. In conclusion, Pb + ions activate erythrocyte K + channels, leading to erythrocyte shrinkage, and also activate the erythrocyte scramblase, leading to phosphatidylserine exposure. The effect could well contribute to the reported decreased life span of circulating erythrocytes during Pb + intoxication.
Type of Medium:
Online Resource
ISSN:
0363-6143
,
1522-1563
DOI:
10.1152/ajpcell.00115.2004
Language:
English
Publisher:
American Physiological Society
Publication Date:
2005
detail.hit.zdb_id:
1477334-X
SSG:
12
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