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

Abstract

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 to 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 to 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.

Pregnancy‐related listeriosis

“…Three separate immunologic phases have been suggested to exist in pregnancy, namely: (a) proinflammatory phase as the blastocyst invades the uterine wall; (b) anti‐inflammatory phase primarily dominated by rapid fetal growth and development; (c) renewed inflammatory phase as the mother prepares to expel the offspring and reject the placenta (Chaouat et al, ; Romero et al, ; Romero et al, ; Mor, ; Dekel et al, ; Mor and Cardenas, ). Therefore, depending on the time of gestation, pregnancy may vary from a proinflammatory to an anti‐inflammatory stage (Saito et al, ; Mor, ; Mor and Cardenas, ; Xu et al, ) and result in varying degrees of susceptibility to L. monocytogenes . Alternatively, listeriosis‐induced increase in T‐cell response when combined with the vulnerability of an underdeveloped fetus could also increase the risk for adverse effects in the fetus (Rowe et al, ; Awofisayo et al, ).…”

Inflammation and pregnancy: the role of the immune system at the implantation site

“…3). 42,43 Inflammation and implantation Embryo implantation, which is an absolute requirement for reproduction, starts with blastocyst apposition to the uterine endometrium, followed by its attachment to the endometrial surface epithelium. Implantation can only take place in a receptive uterus.…”

New Insights into the Relationship between Viral Infection and Pregnancy Complications

“…[22][23][24][25][26] Preeclampsia is diagnosed by the combined presence of hypertension and proteinuria in pregnancy. [27][28][29][30][31] Placental ischemia and hypoxia have been implicated and thought to result from a disorder of deep placentation. 32,33 However, the precise mechanism responsible for this has not been elucidated.Recently, we described a mouse model of viral infection during pregnancy consisting of the injection of the murine herpes virus-68 (MHV-68) early in pregnancy.…”