HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Published online before print November 2, 2004

This Article Full Text (Reprint (PDF)) All Versions of this Article: jlb.0704390v1 77/2/181    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Itagaki, K. Articles by Hauser, C. J. Search for Related Content PubMed PubMed Citation Articles by Itagaki, K. Articles by Hauser, C. J.

© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0704390

Received for publication July 9, 2004.
Revised September 23, 2004.
Accepted for publication October 4, 2004.

Article

Lysophosphatidic acid triggers calcium entry through a nonstore-operated pathway in human neutrophils

The Department of Surgery, Division of Trauma, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark

^@ To whom correspondence should be addressed. E-mail: itagakki{at}umdnj.edu.

	Abstract

Lysophosphatidic acid (LPA) is a bioactive lipid, which is structurally similar to sphingosine 1-phosphate (S1P) and which can mobilize Ca²⁺ in multiple cell types. We recently showed that S1P induces Ca²⁺ entry directly through store-operated Ca²⁺ entry channels in human polymorphonuclear neutrophils (PMN) [1]. We therefore examined the mechanisms by which LPA induces intracellular Ca²⁺ mobilization in PMN. External application of low micromolar LPA caused dose-dependent Ca²⁺ influx without releasing Ca²⁺ stores, whereas G-protein-coupled (GPC) LPA receptors respond to nanomolar LPA. Additive Ca²⁺ influx by LPA compared with 100 nM ionomycin-induced Ca²⁺ influx suggests that LPA-induced Ca²⁺ influx does not pass through store-operated cation (SOC) channels. Ca²⁺ 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 Ca²⁺ influx was inhibited by Gd³⁺, La³⁺, Zn²⁺, or MRS1845 but not by Ni²⁺ 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 Ca²⁺ influx in PMN occurs through a mechanism other than SOC channels, independent of Ca²⁺ store-depletion and S1P synthesis, and that the characteristics of LPA-induced Ca²⁺ 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.

Key Words: bioactive lipid • calcium influx • G-protein-coupled receptors

This article has been cited by other articles:

				S. Brechard and E. J. Tschirhart Regulation of superoxide production in neutrophils: role of calcium influx J. Leukoc. Biol., November 1, 2008; 84(5): 1223 - 1237. [Abstract] [Full Text] [PDF]

				D. J. Kusner, C. R. Thompson, N. A. Melrose, S. M. Pitson, L. M. Obeid, and S. S. Iyer The Localization and Activity of Sphingosine Kinase 1 Are Coordinately Regulated with Actin Cytoskeletal Dynamics in Macrophages J. Biol. Chem., August 10, 2007; 282(32): 23147 - 23162. [Abstract] [Full Text] [PDF]

				S. C. Frasch, K. Zemski-Berry, R. C. Murphy, N. Borregaard, P. M. Henson, and D. L. Bratton Lysophospholipids of Different Classes Mobilize Neutrophil Secretory Vesicles and Induce Redundant Signaling through G2A J. Immunol., May 15, 2007; 178(10): 6540 - 6548. [Abstract] [Full Text] [PDF]

				N. Steinckwich, J.-P. Frippiat, M.-J. Stasia, M. Erard, R. Boxio, C. Tankosic, I. Doignon, and O. Nusse Potent inhibition of store-operated Ca2+ influx and superoxide production in HL60 cells and polymorphonuclear neutrophils by the pyrazole derivative BTP2 J. Leukoc. Biol., April 1, 2007; 81(4): 1054 - 1064. [Abstract] [Full Text] [PDF]

				H. Katayama, Y. Kusaka, H. Yokota, T. Akao, M. Kojima, O. Nakamura, E. Mekada, and E. Mizuki Parasporin-1, a Novel Cytotoxic Protein from Bacillus thuringiensis, Induces Ca2+ Influx and a Sustained Elevation of the Cytoplasmic Ca2+ Concentration in Toxin-sensitive Cells J. Biol. Chem., March 9, 2007; 282(10): 7742 - 7752. [Abstract] [Full Text] [PDF]

				I. Harfi, F. Corazza, S. D'Hondt, and E. Sariban Differential Calcium Regulation of Proinflammatory Activities in Human Neutrophils Exposed to the Neuropeptide Pituitary Adenylate Cyclase-Activating Protein J. Immunol., September 15, 2005; 175(6): 4091 - 4102. [Abstract] [Full Text] [PDF]