Normal pregnancy and preeclampsia both produce inflammatory changes in peripheral blood leukocytes akin to those of sepsis,☆☆,,★★

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Abstract

OBJECTIVE: Our aim was to seek evidence for circulating leukocyte activation in preeclampsia.

STUDY DESIGN: Whole blood flow cytometric techniques were used to analyze surface markers of activation (CD11b, CD14, CD23, CD49d, CD62L, CD64, CD66b, HLA-DR) and intracellular reactive oxygen species. Samples were taken from 21 women with preeclampsia, 21 matched normal pregnant women, 21 healthy nonpregnant controls, and 6 nonpregnant patients with septicemia. Ten preeclamptic cases were followed up 6 weeks post partum.

RESULTS: The leukocytes of healthy pregnant women differed substantially and significantly from those of nonpregnant women (increased CD11b, CD14, and CD64 and increased intracellular reactive oxygen species). In preeclampsia there was, in addition to these changes, reduced expression of l-selectin and further increases in intracellular reactive oxygen species. The changes found in normal pregnancy and preeclampsia were similar, but not identical, to those found in sepsis.

CONCLUSIONS: Normal third-trimester pregnancy is characterized by remarkable activation of peripheral blood leukocytes, which is further increased in preeclampsia. (Am J Obstet Gynecol 1998;179:80-6.)

Section snippets

Material and methods

Peripheral venous blood sampled by use of a syringe was immediately added to anticoagulant, either 10 μg/mL leupeptin, a protease inhibitor (Sigma, Poole, United Kingdom) for surface antigen analysis, or 10 IU/mL preservative-free heparin (Sigma) for measurement of intracellular reactive oxygen species. The anticoagulated blood was processed and analyzed within 45 minutes of venipuncture.

Whole blood was analyzed flow cytometrically with use of the fluorescent nuclear vital dye LDS-751

Results

Granulocytes and monocytes from normal pregnant women, women with preeclampsia, and patients with sepsis all showed significantly higher surface expression of CD11b and CD64 compared with the normal nonpregnant control women. Surface expression of l-selectin on granulocytes was significantly reduced in samples from preeclamptic women and cases with sepsis but not normal pregnant women. Normal pregnancy was characterized by significantly higher expression of CD14 on both monocytes and

Comment

The isolation of leukocytes from whole blood may cause activation and artifactual differences not present in vivo.9 Hence we used whole blood flow cytometry, which produces less in vitro activation than does conventional density gradient centrifugation or red blood cell lysis.10 The fluorescent vital nucleic acid dye LDS-751 allowed nucleated leukocytes to be differentiated from nonnucleated erythrocytes.7 Because the cells were unfixed, intracellular reactive oxygen species, which are a

Acknowledgements

We thank Staff Midwife Davina Buckley and Dr Mark Juniper for help in recruiting normal pregnant women and septic patients, respectively.

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    From the Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital.

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    Supported by Action Research and Oxford Regional Health Authority (G.P.S.) and the Soros Foundation (K.S.).

    Reprint requests: Gavin P. Sacks, MD, Nuffield Department of Obstetrics and Gynaecology, John Radcliffe Hospital, Oxford, United Kingdom OX3 9DU.

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