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Participation of leukotriene C4 in the regulation of suicidal erythrocyte death

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Foller M., Mahmud H., Gu S., Wang K., Floride E., Kucherenko Y., Luik S., Laufer S., Lang F.

Journal of Physiology and Pharmacology

2009

tom 60

nr 3

135-143

Eryptosis, the suicidal death of erythrocytes, is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine exposure at the erythrocyte surface. Eryptosis is triggered by increase in cytosolic Ca2+ concentration upon energy depletion. The present study explored the involvement of leukotrienes. Western blotting was employed to detect the cysteinyl-leukotriene receptor cysLT1, competitive immune assay to determine leukotriene release from erythrocytes, Fluo3 fluorescence to estimate cytosolic Ca2+ concentration, forward scatter to analyse cell volume and annexin V-binding to disclose phosphatidylserine exposure. As a result, erythrocytes expressed the leukotriene receptor CysLT1. Glucose depletion (24 hours) significantly increased the formation of the cysteinyl-leukotrienes C4/D4/E4. Leukotriene C4 (10 nM) increased Ca2+ entry, decreased forward scatter, activated caspases 3 and 8, and stimulated annexin V-binding. Glucose depletion similarly increased annexin V-binding, an effect significantly blunted in the presence of the leukotriene receptor antagonist cinalukast (1 µM) or the 5-lipoxygenase inhibitor BW B70C (1 µM). In conclusion, upon energy depletion erythrocytes form leukotrienes, which in turn activate cation channels, leading to Ca2+ entry, cell shrinkage and cell membrane scrambling. Cysteinyl-leukotrienes thus participate in the signaling of eryptosis during energy depletion.

Ograniczanie wyników

1 Journal of Physiology and Pharmacology

1 Floride E.

1 Foller M.

1 Gu S.

1 Kucherenko Y.

1 Lang F.

1 Laufer S.

1 Luik S.

1 Mahmud H.

1 Wang K.

1 2009

Wyniki wyszukiwania

Participation of leukotriene C4 in the regulation of suicidal erythrocyte death