High capacity for leukotriene biosynthesis in peripheral blood during pregnancy

Abstract

Pregnancy is accompanied by major immunological changes to maintain both tolerance for the fetus and immune competence. Leukotrienes are powerful 5-lipoxygenase-derived inflammatory mediators and the characteristics of leukotriene-related diseases (e.g., asthma, allergic rhinitis) change during pregnancy. Here, we show that pregnancy affects leukotriene synthesis in human blood and leukocytes. 5-Lipoxygenase product formation in stimulated blood of pregnant women was significantly higher than in non-pregnant females. Although a pregnancy-related increase in neutrophil and monocyte counts may explain these observations, granulocytes of pregnant donors have lower leukotriene-synthetic capacities. On the other hand, granulocytes from non-pregnant woman produced more leukotrienes when resuspended in plasma of pregnant women than of non-pregnant females. Together, we show that leukotriene biosynthesis in maternal blood is increased by the interrelations of higher leukocyte numbers, lower cellular capacity for leukotriene synthesis and stimulatory effects of plasma. This bias may affect leukotriene-related diseases during pregnancy and their pharmacological treatment.

Keywords: 12(S)-hydroxy-5-cis-8,10-trans-heptadecatrienoic acid; 12-HHT; 5(S)-hydro(pero)xy-6-trans-8,11,14-cis-eicosatetraenoic acid; 5-H(P)ETE; 5-LO; 5-lipoxygenase; AA; COX; EDTA; ESI; HPLC; LPS; LT; LTRA; PBMC; PBS; PBS plus 1mg/ml glucose; PBS plus 1mg/ml glucose plus 1mM CaCl(2); PG buffer; PGC buffer; PMNL; ROS; SDS-PAGE; SEM; UPLC-MS/MS; arachidonic acid; cyclooxygenase; electrospray ionization; ethylenediaminetetraacetate; fMLP; formyl-methionyl-leucyl-phenylalanine; high performance liquid chromatography; inflammation; leukotriene; leukotriene receptor antagonist; leukotrienes; lipopolysaccharide; lipoxygenase; peripheral blood mononuclear cells; phosphate buffered saline; polymorphonuclear leukocytes; pregnancy; reactive oxygen species; sodium dodecyl sulfate polyacrylamide gel electrophoresis; standard error of the mean; ultra high performance liquid chromatography tandem mass spectrometry.