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PLACENTAL ISCHEMIA TRIGGERS IMMUNE ACTIVATION AS LEUKOCYTE OVERPRODUCTION OF SFlt‐1: A STEP IN THE PATHOGENESIS OF PREECLAMPSIA?
Author(s) -
Wallace Kedra,
Rutland Sarah,
TamTam Kiran,
Weimer Abram,
Martin James N,
LaMarca Babbette
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.793.12
Subject(s) - preeclampsia , medicine , soluble fms like tyrosine kinase 1 , endocrinology , perfusion , blood pressure , ischemia , immune system , pathogenesis , mean arterial pressure , pregnancy , andrology , immunology , biology , placental growth factor , heart rate , genetics
Plasma, amniotic fluid, and placental soluble fms‐like tyrosine kinase (sFlt‐1) mRNA is increased in patients with preeclampsia. We and others have shown placental ischemia (PI), TNF alpha and agonistic autoantibodies to the angiotensin II type I receptor are important stimuli for sFlt‐1 production during pregnancy. The objective of this study was to determine if leukocytes stimulated in rats with PI are a source of circulating sFlt‐1. Sprague‐Dawley rats were anesthetized on day 14 of pregnancy and underwent either examination under anesthesia (NP) or reduced uterine perfusion pressure (RUPP). Rats were instrumented with a carotid catheter for arterial pressure measurement (MAP) on day 19. Plasma was collected and leukocytes isolated and cultured overnight in RPMI containing, 1.022 ng/ml IL‐2 and 4 ng/ml IL‐12 at 5% CO2 and 37°C. Cell culture media was removed and ELISA utilized to determine sFlt‐1. MAP increased from 102 +/− 1 mmHg in NP rats to 127 +/− 2 mmHg in RUPP rats. Circulating sFlt‐1 was 963 pg/ml in NP rats vs 1493 pg/ml in RUPP rats. In addition, sFlt‐1 from NP PBL culture was 30+/−8 pg/ml while RUPP sFlt‐1 PBL culture increased significantly to 88+/−20 pg/ml (P <0.01) The mechanisms whereby sFlt‐1 over expression occurs during preeclampsia are not well defined. This study demonstrates that immune cells activated response to PI are a source for excess sFlt‐1.