Increased neutrophil-endothelial adhesion induced by placental factors is mediated by platelet-activating factor in preeclampsia.
OBJECTIVE
Endothelial cell activation or dysfunction and neutrophil-endothelial cell adhesion have been suggested to be important in the pathophysiology of preeclampsia. However, the mechanisms that underlie the alteration of endothelial cell function in preeclampsia are unknown. Placenta from preeclamptic pregnancies produces mediators and autacoids, which may be released into the maternal circulation and modulate endothelial function. In this study, the effect of placental factor(s) on neutrophil-endothelial adhesion and the possible role of platelet-activating factor (PAF) in mediating the response have been examined.


METHODS
Endothelial cells were isolated from human umbilical veins (HUVECs) from normal pregnancies. Confluent primary passage HUVECs were exposed to conditioned medium derived from normal and preeclamptic placental tissue cultures, with unconditioned medium as a control. Placental-conditioned medium was prepared by incubation of placental whole villous tissue in Dulbecco's Modified Eagle's Medium (DMEM) for 48 hours. Neutrophil-endothelial adhesion assays were performed to evaluate placental factors in mediating neutrophil-endothelial adhesion, and a PAF-3H scintillation proximity assay (SPA) system was used to determine endothelial PAF production. The PAF-receptor antagonist WEB 2086 was used to block placental factor-mediated increased neutrophil-endothelial adhesion induced by conditioned medium derived from preeclamptic placenta.


RESULTS
Neutrophils were significantly more adherent to HUVECs treated with conditioned medium from preeclamptic placentas (28.44 +/- 2.47%) than to HUVECs treated with conditioned medium from normal placentas (18.95 +/- 1.57%) or with unconditioned medium (14.60 +/- 1.29%, P < .01). Also, HUVECs exposed to preeclamptic placental-conditioned medium produced more PAF than the cells exposed to normal conditioned medium and unconditioned medium, 416.18 +/- 17.14 pg/1 x 10(7) cells versus 330.90 +/- 35.70 and 296.43 +/- 44.40 pg/1 x 10(7) cells, P < .05, respectively. The PAF receptor antagonist WEB 2086 completely blocked increased neutrophil-endothelial adhesion induced by preeclamptic placental-conditioned medium (13.24 +/- 0.81% versus 31.31 +/- 4.75%, P < .01).


CONCLUSIONS
In preeclampsia, the placenta releases one or more factors promoting neutrophil-endothelial adhesion. The increased neutrophil-endothelial adhesion thereby induced is a PAF-mediated event. It is suggested that if preeclamptic placentas release toxic factors into the maternal circulation in vivo, these factors may contribute to the altered vascular endothelial cell function in preeclampsia.
Wang
Y
Y
Department of Obstetrics and Gynecology, Louisiana State University Medical Center, Shreveport 71130, USA. ywang1@lsumc.edu
Adair
C D
CD
Weeks
J W
JW
Lewis
D F
DF
Alexander
J S
JS
D001381:Azepines / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D005260:Female; D006801:Humans; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects; D010920:Placenta / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000096:biosynthesis / Q000502:physiology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D011225:Pre-Eclampsia / Q000378:metabolism* / Q000473:pathology*; D011247:Pregnancy; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles / Q000494:pharmacology
D001381:Azepines; D017077:Culture Media, Conditioned; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles; C039351:platelet activating factor receptor; C052518:WEB 2086