Maternal autoantibodies from preeclamptic patients activate angiotensin receptors on human mesangial cells and induce interleukin-6 and plasminogen activator inhibitor-1 secretion.
BACKGROUND
Preeclampsia affects 3-5% of all pregnancies. It is a major cause of maternal and fetal morbidity and mortality. Recent studies demonstrate that autoantibodies against the angiotensin II type 1 (AT(1)) receptor are present in the serum of preeclamptic patients. In this study, we investigated the role of AT(1) receptor-agonistic autoantibody (AT1-AA) regarding interleukin-6 (IL-6) and plasminogen activator inhibitor-1 (Pai-1) secretion in human mesangial cells.


METHODS
The study included ten patients: five severely preeclamptic and five normotensive pregnant women. Immunoglobulin-G (IgG) was purified from each individual. The presence of AT1-AA was determined based on its ability to stimulate an increase in the contraction rate of rat neonatal cardiomyocytes. Primary human mesangial cells were chosen to study IgG-induced secretion of IL-6 and Pai-1. Losartan and epitope peptides were used to determine whether AT1-AA interaction with AT(1) receptor was associated with stimulation of IL-6 and Pai-1 secretion and was mediated through AT(1) receptor activation.


RESULTS
The IgG from preeclamptic patients stimulated an increased contraction rate in rat neonatal cardiomyocytes. The IgG from preeclamptic patients induced the AT(1) receptor-specific secretion of IL-6 and Pai-1 from human mesangial cells at a significantly higher level than that achieved with IgG from normotensive patients. Competition with an epitope peptide suggested that the AT(1) receptor was stimulated by AT1-AA.


CONCLUSIONS
Our findings suggest that a maternal autoantibody with the ability to activate AT(1) receptors may account for the development of renal damage seen in preeclamptic patients.
Bobst
Sol M
SM
Department of Biochemistry and Molecular Biology, University of Texas at Houston Medical School, 6431 Fannin, Houston, TX 77030, USA.
Day
Mary-Clare
MC
Gilstrap
Larry C
LC
Xia
Yang
Y
Kellems
Rodney E
RE
D000818:Animals; D001323:Autoantibodies / Q000097:blood / Q000494:pharmacology*; D002478:Cells, Cultured; D005260:Female; D005920:Glomerular Mesangium / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D007674:Kidney Diseases / Q000209:etiology / Q000276:immunology; D032383:Myocytes, Cardiac / Q000166:cytology; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000209:etiology / Q000276:immunology*; D011247:Pregnancy; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000276:immunology* / Q000378:metabolism
D001323:Autoantibodies; D015850:Interleukin-6; D017395:Plasminogen Activator Inhibitor 1; D044140:Receptor, Angiotensin, Type 1