Biochimica et Biophysica Acta. Molecular Cell Research vol:1793 issue:6 pages:1041-1049
Extracellular agonists increase the cytosolic free Ca(2+) concentration ([Ca(2+)](c)) by Ca(2+) influx and by stimulating Ca(2+) release from intracellular stores, mainly the endoplasmic reticulum and to a lesser extent also later compartments of the secretory pathway, particularly the Golgi. The Golgi takes up Ca(2+) via Sarco/Endoplasmic Reticulum Ca(2+)ATPases (SERCAs) and the Secretory-Pathway Ca(2+)ATPases (SPCAs). The endogenous expression of SERCAs and SPCAs neutrophils was demonstrated by Western blotting and immunocytochemistry. Up till now, all cytosolic Ca(2+) transients due to intracellular Ca(2+) release have been found to originate from SERCA-dependent stores. We found that human neutrophils also present Ca(2+) release from a SERCA-independent store. Changes in [Ca(2+)](c) of neutrophils were investigated during chemokinesis induced by chemotactic factors in Ca(2+)-free solution with and without the SERCA-specific inhibitor thapsigargin. Using N-formyl-methionyl-leucyl-phenylalanine or interleukin-8 as agonists, Ca(2+) release from intracellular stores was observed in respectively about 40% and 20% of the neutrophils pre-treated with Ca(2+)-free solution and thapsigargin. In the latter condition, 20-30% of the cells preserved migratory behaviour. These results indicate that both SERCA-dependent and SERCA-independent (presumably SPCA-dependent) intracellular Ca(2+) stores contribute to Ca(2+) signaling during chemokinesis of human neutrophil granulocytes.