Lack of proinflammatory effects of free fatty acids on human umbilical cord vein endothelial cells and leukocytes.

AIM: To determine whether the free fatty acids (FFAs), oleic, linoleic, and palmitic acid, found elevated before 20 weeks of pregnancy in those women who later develop preeclampsia, induced changes in expression of the vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), or E-selectin in cultured human umbilical cord vein endothelial cells (HUVEC), and integrin subunit CD11b, L-selectin or intracellular reactive oxygen species (ROS) in leukocytes. METHODS: The VCAM-1, ICAM-1, and E-selectin expression were measured using ELISA in HUVEC after incubation with 100 micromol of either oleic, linoleic, or palmitic acid for 6 hr and 24 hr. The co-reactivity with lipopolysaccharide (LPS), the amount of VCAM-1 mRNA in the cells, and soluble VCAM-1 in the incubation medium were measured as well. Leukocyte adhesion molecules and ROS were measured after incubation with 750 microm of either of the FFAs in a whole blood model using flow cytometry. RESULTS: No effects of the FFAs tested were found on the HUVEC or leukocyte adhesion molecule expression or intracellular ROS. The only exception to this was palmitic acid incubation, which significantly lowered the VCAM-1 expression in HUVEC after 24-hr incubation and also slowed the decay of VCAM-1 expressed after stimulation with LPS. CONCLUSIONS: The lack of significant proinflammatory changes of the FFAs tested might indicate that the elevated plasma levels of FFAs seen in preeclampsia most probably are products of the preeclamptic process rather than a causative factor.

Calprotectin plasma level is elevated in preeclampsia.

BACKGROUND: Calprotectin is a protein found in myelomonocytic cells and plays a role in various physiological functions such as inflammatory processes and antiproliferation of cells, and in the neutrophil defense against bacterial infections. Preeclampsia is characterized by maternal endothelial dysfunction and by insufficient trophoblast invasion into the maternal endometrium (decidua). In addition, preeclampsia is associated with maternal leukocyte activation and we therefore wanted to investigate whether calprotectin levels in plasma from women with preeclampsia differed from the levels in normotensive pregnant and nonpregnant women. METHOD: Calprotectin measurements were included in a case-control study of 20 preeclamptic women matched with 20 normotensive pregnant women regarding age, pregnancy length, parity and body mass index (BMI). We also measured calprotectin in 12 nonpregnant women. Calprotectin plasma levels were analyzed using an enzyme-linked immunosorbent assay (ELISA). RESULTS: We discovered significantly elevated plasma calprotectin levels in preeclamptic patients compared to matched normotensive pregnancies: 768 (612-1016) microg/L vs. 445 (276-598) microg/L (medians, 25, 75 percentiles, respectively), p = 0.002. CONCLUSIONS: The elevated plasma calprotectin levels demonstrated in the preeclampsia group supports the notion that leukocytes are activated in preeclampsia. The elevated calprotectin level might constitute a part of the innate defense in myelomonocytic cells against microorganisms in pregnancy. We suggest further elucidation of a role for calprotectin in the development of pregnancy disorders such as preeclampsia.

Leukocyte adhesion molecules and reactive oxygen species in preeclampsia.

OBJECTIVE: The aim of our study was to compare the expression of leukocyte adhesion molecules, intracellular reactive oxygen species, and vasoactive substances in preeclampsia and matched normotensive pregnancies and to explore differences between pregnancy and the nonpregnant state regarding these parameters. METHODS: Flow cytometry was used to analyze the monocyte and granulocyte expression of adhesion molecules from 20 matched pairs of preeclampsia/normotensive pregnancies and 12 nonpregnant subjects. Basal levels of CD11b, CD11c, CD62L, and CD14 were measured. In addition, expression of human lymphocyte antigen-DR, CD4, CD8, and CD4/CD8 ratio were assessed. Basal reactive oxygen species levels, as well as reactivity upon in vitro stimulation with phorbol 12-myristate 13-acetate, were measured in monocytes and granulocytes with the probes dihydroethidium, dichlorofluorescein-diacetate, and dihydrorhodamine-123. Further, the plasma levels of endothelin-1, the nitric oxide metabolites nitrite/nitrate, and total antioxidant status were analyzed. RESULTS: Monocytes expressed significantly higher levels of CD11b and CD14 in preeclamptic patients compared with normotensive pregnant subjects, whereas CD11c was elevated on both monocytes and granulocytes in pregnancy compared with the nonpregnant state. Both monocytes and granulocytes displayed higher basal, as well as phorbol 12-myristate 13-acetate-stimulated, amounts of reactive oxygen species in the preeclampsia group compared with the normotensive group. We also found the endothelin-1 and antioxidant levels significantly elevated in preeclampsia patients compared with normotensive subjects, whereas no differences were seen between the groups regarding nitrite/nitrate levels. CONCLUSION: These results show that the maternal blood leukocytes are activated in preeclampsia and support the view that oxidative stress is a contributing factor in the pathophysiology of preeclampsia.