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Lysophosphatidic acid triggers calcium entry through a non‐store‐operated pathway in human neutrophils
Author(s) -
Itagaki Kiyoshi,
Kannan Kolenkode B.,
Hauser Carl J.
Publication year - 2005
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.0704390
Subject(s) - lysophosphatidic acid , biology , calcium , microbiology and biotechnology , calcium signaling , immunology , biochemistry , signal transduction , medicine , receptor
Lysophosphatidic acid (LPA) is a bioactive lipid, which is structurally similar to sphingosine 1‐phosphate (S1P) and which can mobilize Ca 2 + in multiple cell types. We recently showed that S1P induces Ca 2 + entry directly through store‐operated Ca 2 + entry (SOCE) channels in human polymorphonuclear neutrophils (PMN) [ 1 ]. We therefore examined the mechanisms by which LPA induces intracellular Ca 2 + mobilization in PMN. External application of low micromolar LPA caused dose‐dependent Ca 2 + influx without releasing Ca 2 + stores, whereas G‐protein‐coupled (GPC) LPA receptors respond to nanomolar LPA. Additive Ca 2 + influx by LPA compared with 100 nM ionomycin‐induced Ca 2 + influx suggests that LPA‐induced Ca 2 + influx does not pass through SOCE channels. Ca 2 + influx was resistant to inhibition of G i/o by pertussis toxin, of phospholipase C by U73122, and of G 12/13 / Rho by Y27632, all demonstrating GPC receptor independence. This Ca 2 + influx was inhibited by Gd 3 + , La 3 + , Zn 2 + , or MRS1845 but not by Ni 2 + or the sphingosine kinase inhibitor dimethylsphingosine. In addition, we found that LPA has no effect on neutrophil chemotaxis; however, it has stimulatory effects on neutrophil respiratory burst in a dose‐response manner. These findings suggest that LPA‐induced Ca 2 + influx in PMN occurs through a mechanism other than SOCE channels, independent of Ca 2 + store‐depletion and S1P synthesis, and that the characteristics of LPA‐induced Ca 2 + influx are similar to those of S1P‐induced influx in terms of sensitivity to inorganic inhibitors. Unlike S1P, LPA has stimulatory effects on neutrophil respiratory burst.