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Leukocyte Pyruvate Kinase Expression is Reduced in Normal Human Pregnancy but not in Pre-eclampsia

Authors

  • Yi Xu,

    1. Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA
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  • Sally A. Madsen-Bouterse,

    1. Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) of NIH, Bethesda, MD and Detroit, MI, USA
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  • Roberto Romero,

    1. Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA
    2. Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) of NIH, Bethesda, MD and Detroit, MI, USA
    3. Center of Molecular Medicine and Genetics, Hutzel Women’s Hospital at the Detroit Medical Center, Wayne State University, Detroit, MI, USA
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  • Sonia Hassan,

    1. Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA
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  • Pooja Mittal,

    1. Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA
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  • Megan Elfline,

    1. Department of Ophthalmology and Visual Sciences, The University of Michigan Medical School, Ann Arbor, MI, USA
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  • Aiping Zhu,

    1. Department of Ophthalmology and Visual Sciences, The University of Michigan Medical School, Ann Arbor, MI, USA
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  • Howard R. Petty

    1. Department of Ophthalmology and Visual Sciences, The University of Michigan Medical School, Ann Arbor, MI, USA
    2. Department of Microbiology and Immunology, The University of Michigan Medical School, Ann Arbor, MI, USA
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Dr Howard R. Petty, Department of Ophthalmology and Visual Sciences, 1000 Wall Street, The University of Michigan Medical School, Ann Arbor, MI 48105, USA.
E-mail: hpetty@umich.edu

Abstract

Citation Xu Y, Madsen-Bouterse SA, Romero R, Hassan S, Mittal P, Elfline M, Zhu A, Petty HR. Leukocyte pyruvate kinase expression is reduced in normal human pregnancy but not in pre-eclampsia. Am J Reprod Immunol 2010; 64: 137–151

Problem  Emerging evidence suggests that metabolism influences immune cell signaling and immunoregulation. To examine the immunoregulatory role of glycolysis in pregnancy, we evaluated the properties of pyruvate kinase in leukocytes from non-pregnant women and those with normal pregnancy and pre-eclampsia.

Method of study  We evaluated pyruvate kinase expression in lymphocytes and neutrophils from non-pregnant, pregnant, and pre-eclampsia patients using fluorescence microscopy and flow cytometry. Leukocyte pyruvate kinase activity and pyruvate concentrations were also evaluated. To study pyruvate’s effect on signaling, we labeled Jurkat T cells with Ca2+ dyes and measured cell responses in the presence of agents influencing intracellular pyruvate.

Results  The expression of pyruvate kinase is reduced in lymphocytes and neutrophils from normal pregnant women in comparison with those of non-pregnant women and pre-eclampsia patients. Similarly, the activity of pyruvate kinase and the intracellular pyruvate concentration are reduced in leukocytes of normal pregnant women in comparison with non-pregnant women and women with pre-eclampsia. Using Jurkat cells as a model of leukocyte signaling, we have shown that perturbations of intracellular pyruvate influence Ca2+ signals.

Conclusion  Normal pregnancy is characterized by reduced pyruvate kinase expression within lymphocytes and neutrophils. We speculate that reduced pyruvate kinase expression modifies immune cell responses due to reduced pyruvate concentrations.

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