Dual effects of lysophosphatidic acid on human airway smooth muscle cell proliferation and survival.
Lysophosphatidic acid (LPA) is a phospholipid growth mediator found in serum at 2-20 microM. In many cell types, including human airway smooth muscle (HASM) cells, LPA-induced proliferation occurs at 10-100 microM 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 microM LPA stimulated HASM cell mitogenesis. However, with 100 microM 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 microM LPA solution in Ca2+ free medium contained markedly greater bioactivity than a 100 microM 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.
Department of Pharmacology, University of Nebraska Medical Center, Omaha, NE 68198-6260, USA.
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D017209:Apoptosis; D002118:Calcium / Q000032:analysis; D002455:Cell Division; D002470:Cell Survival; D002478:Cells, Cultured; D003470:Culture Media / Q000737:chemistry; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology*; D008934:Mitogens / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000187:drug effects*; D014132:Trachea / Q000187:drug effects
D003470:Culture Media; D008246:Lysophospholipids; D008934:Mitogens; D002118:Calcium