Dual effects of lysophosphatidic acid on human airway smooth muscle cell proliferation and survival

Tracy L. Ediger, Myron L. Toews

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Lysophosphatidic acid (LPA) is a phospholipid growth mediator found in serum at 2-20 μM. In many cell types, including human airway smooth muscle (HASM) cells, LPA-induced proliferation occurs at 10-100 μM LPA. At these concentrations LPA forms Ca2+ precipitates. The potential involvement of Ca2+ and Ca2+-LPA precipitates in LPA-induced HASM cell mitogenesis was investigated. In the absence of extracellular Ca2+, 10 and 30 μM LPA stimulated HASM cell mitogenesis. However, with 100 μM LPA in the absence of extracellular Ca2+, HASM cells exhibited a profound shape change and loss of viability, determined to be apoptosis by both DNA staining and assessment of cytosolic nucleosomal reactivity. A bioassay based on the adenosine 3′:5′-cyclic monophosphate response of C62B rat glioma cells was used to measure the bioactivity of LPA solutions prepared in Ca2+-free and Ca2+-containing medium. After 24 h, a 100 μM LPA solution in Ca2+-free medium contained markedly greater bioactivity than a 100 μM LPA solution made in Ca2+-containing medium. In summary, formation of Ca2+-LPA precipitates decreases the amount of biologically active LPA in solution, and high concentrations of bioactive LPA achieved in Ca2+-free but not in Ca2+-containing medium induce apoptosis of HASM cells.

Original languageEnglish (US)
Pages (from-to)59-67
Number of pages9
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1531
Issue number1-2
DOIs
StatePublished - Mar 30 2001

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Keywords

  • Airway smooth muscle cell
  • Apoptosis
  • Extracellular Ca
  • Lysophosphatidic acid
  • Proliferation

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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