Effect of lysophospholipids on signaling in the human Jurkat T cell line

Yan Xu, Graham Casey, Gordon B. Mills

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

Lysophospholipids have recently been demonstrated to induce activation and proliferation of fibroblasts and other cell lineages by interacting with high affinity cell surface receptors reading to specific intracellular signaling events. Platelet activation, likely at the site of injury or inflammation, results in increased production of lysophospholipids suggesting a possible source of lysophospholipids. We have recently demonstrated that high concentrations of lysophospholipids are present in ascites and plasma from ovarian cancer patients, suggesting that physiologically produced lysophospholipids could interact with cells present in these fluids, including lymphocytes, and alter their function. We demonstrate herein that lysophosphatidic acid (LPA), lysophosphatidylserine (LPS), and sphingosylphosphorylcholine (SPC) activate the Jurkat T cell line. Each of the lysophospholipids induced a transient increase in cytosolic free calcium ([Ca2+](i) in Jurkat cells. Increases in [Ca2+](i) were cross-desensitized by LPA, LPS and SPC, suggesting that the lysophospholipids share the same receptor(s) or that their downstream signaling pathways converge or interact. Lysophosphatidylgycerol (LPG), a competitive inhibitor of the putative LPA receptor, inhibited the calcium releasing activity of LPA, but not that of LPS and SPC, suggesting that these lysophospholipids interact with different receptors and that desensitization is due to interactions in downstream signaling pathways. The ability of the lysophospholipids to induce increases in [Ca2+](i) was attenuated, but not completely blocked, by increases in [Ca2+](i) induced by activation of the thrombin receptor. In contrast, increases in [Ca2+](i) induced by the lysophospholipids and cross-linking the CD3 component of the T cell receptor complex with the UCHT1 antibody did not undergo heterologous desensitization. Strikingly, LPA is sufficient to stimulate proliferation of Jurkat cells in serum-free medium or in synergy with low concentrations of fetal bovine serum. in addition, LPA also increased the production of the T cell growth factor, interleukin 2 (IL-2), by Jurkat cells treated with phorbol esters. LPS, in contrast, inhibited Jurkat proliferation while increasing IL-2 production and SPC inhibited both processes. Thus, although all three lysophospholipids were sufficient to induce a transient increase in [Ca2+](i) in Jurkat cells, they induced markedly different physiological consequences.

Original languageEnglish (US)
Pages (from-to)441-450
Number of pages10
JournalJournal of Cellular Physiology
Volume163
Issue number3
DOIs
StatePublished - Jun 1995
Externally publishedYes

Fingerprint

Lysophospholipids
Jurkat Cells
T-cells
T-Lymphocytes
Cell Line
Interleukin-2
Chemical activation
Lysophosphatidic Acid Receptors
Thrombin Receptors
Calcium
Lymphocytes
Serum-Free Culture Media
Platelet Activation
Cell Surface Receptors
Phorbol Esters
Cell Lineage
Fibroblasts
T-Cell Antigen Receptor
Platelets
Ascites

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Effect of lysophospholipids on signaling in the human Jurkat T cell line. / Xu, Yan; Casey, Graham; Mills, Gordon B.

In: Journal of Cellular Physiology, Vol. 163, No. 3, 06.1995, p. 441-450.

Research output: Contribution to journalArticle

Xu, Yan ; Casey, Graham ; Mills, Gordon B. / Effect of lysophospholipids on signaling in the human Jurkat T cell line. In: Journal of Cellular Physiology. 1995 ; Vol. 163, No. 3. pp. 441-450.
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