The implication of aberrant GM-CSF expression in decidual cells in the pathogenesis of preeclampsia.
Preeclampsia is characterized by an exaggerated systemic inflammatory state as well as shallow placentation. In the decidual implantation site, preeclampsia is accompanied by an excessive number of both macrophages and dendritic cells as well as their recruiting chemokines, which have been implicated in the impairment of endovascular trophoblast invasion. Granulocyte-macrophage colony-stimulating factor is known to regulate the differentiation of both macrophages and dendritic cells, prompting both in vivo and in vitro evaluation of granulocyte-macrophage colony-stimulating factor expression in human decidua as well as in a mouse model of preeclampsia. This study revealed increased granulocyte-macrophage colony-stimulating factor expression levels in preeclamptic decidua. Moreover, both tumor necrosis factor-α and interleukin-1 β, cytokines that are implicated in the genesis of preeclampsia, markedly up-regulated granulocyte-macrophage colony-stimulating factor production in cultured first-trimester human decidual cells. The conditioned media of these cultures promoted the differentiation of both macrophages and dendritic cells from a monocyte precursor. Evaluation of a murine model of preeclampsia revealed that the decidua of affected animals displayed higher levels of immunoreactive granulocyte-macrophage colony-stimulating factor as well as increased numbers of both macrophages and dendritic cells when compared to control animals. Because granulocyte-macrophage colony-stimulating factor is a potent inducer of differentiation and activation of both macrophages and dendritic cells, these findings suggest that this factor plays a crucial role in the pathogenesis of preeclampsia.
Huang
S Joseph
SJ
Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, P.O. Box 208063, New Haven, CT 06520-8063, USA. joseph.huang@yale.edu
Zenclussen
Ana C
AC
Chen
Chie-Pein
CP
Basar
Murat
M
Yang
Hui
H
Arcuri
Felice
F
Li
Min
M
Kocamaz
Erdogan
E
Buchwalder
Lynn
L
Rahman
Mizanur
M
Kayisli
Umit
U
Schatz
Frederick
F
Toti
Paolo
P
Lockwood
Charles J
CJ
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D003656:Decidua / Q000166:cytology* / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000166:cytology / Q000502:physiology; D010920:Placenta / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D011225:Pre-Eclampsia / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology*; D011247:Pregnancy; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor