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PAF‐mediated Ca 2 + influx in human neutrophils occurs via store‐operated mechanisms
Author(s) -
Hauser Carl J.,
Fekete Zoltan,
Adams John M.,
Garced Matthew,
Livingston David H.,
Deitch Edwin A.
Publication year - 2001
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.69.1.63
Subject(s) - calcium , thapsigargin , inflammation , microbiology and biotechnology , calcium metabolism , biology , pharmacology , endocrinology , medicine , chemistry , immunology
Many inflammatory mediators activate neutrophils (PMN) partly by increasing cytosolic calcium concentration ([Ca 2 + ] i ). Modulation of PMN [Ca 2 + ] i might therefore be useful in regulating inflammation after shock or sepsis. The hemodynamic effects of traditional Ca 2 + channel blockade, however, could endanger unstable patients. Store‐operated calcium influx (SOCI) is known now to contribute to Ca 2 + flux in “nonexcitable” cells. Therefore, we studied the role of SOCI in human PMN responses to the proinflammatory ligand PAF. PMN [Ca 2 + ] i was studied by spectrofluorometry with and without external calcium. We studied the effects of PAF on Mn 2 + entry into and on Ca 2 + efflux from thapsigargin (Tg)‐treated cells. Influx was assessed in the presence and absence of the blockers SKF‐96365 (SKF), TMB‐8, and 2‐APB. Half of PAF [Ca 2 + ] i mobilization occurs via calcium influx. The kinetics of calcium entry were typical of SOCI rather than receptor‐mediated calcium entry (RMCE). SKF had multiple nonspecific effects on [Ca 2 + ] i . Inhibition of store emptying by TMB‐8 and 2‐APB blocked all calcium entry, demonstrating influx was store depletion‐dependent. PAF has no direct effect on calcium efflux. Where SOCI is maximal, PAF has no further effect on calcium‐channel traffic. PAF‐induced calcium signals are highly dependent on SOCI and independent of RMCE. SOCI‐specific blockade might modulate PMN‐mediated inflammation and spare cardiovascular function in shock and sepsis.