Innate immune response by ficolin binding in apoptotic placenta is associated with the clinical syndrome of preeclampsia.
BACKGROUND
Unidentified circulating factors derived from placenta are thought to be responsible for the exaggerated systemic inflammation leading to preeclampsia. Our aim was to identify the circulating factors present in preeclampsia and to investigate their relationship to the underlying systemic immune response responsible for the associated clinical manifestations.


METHODS
We obtained blood samples from pregnant women with and without preeclampsia and performed comparative proteomic analyses to identify the abnormal circulating factors by 2-dimensional polyacrylamide gel electrophoresis and matrix-assisted laser desorption ionization time of flight for protein separation and identification. In placentas from preeclamptic pregnancies, we evaluated the potential role of the candidate proteins identified by Western and immunohistochemical analysis. We also used proinflammatory cytokine antibody arrays to investigate local and systemic immune responses.


RESULTS
We found that ficolins, the pattern-recognition proteins involved in the lectin-complement pathway, were differentially expressed in plasma from preeclamptic pregnancies. Ficolins were present in low concentrations in plasma but at high concentrations in the placenta, particularly in syncytiotrophoblasts undergoing apoptosis. The binding of ficolins in apoptotic trophoblasts induced innate immunity through local and systemic cytokine activation and correlated with the clinical manifestation of preeclampsia.


CONCLUSIONS
We identified specific in vivo circulating factors derived from the placenta that are responsible for the local immune recognition and systemic inflammatory response in the development of clinical manifestations of preeclampsia. These findings may have predictive value and also therapeutic applications to lessen adverse clinical outcomes of preeclampsia.
Wang
Chi Chiu
CC
Li Ka Shing Institute of Health Sciences, Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong, SAR. ccwang@cuhk.edu.hk
Yim
Ka Wing
KW
Poon
Terence C W
TC
Choy
Kwong Wai
KW
Chu
Ching Yan
CY
Lui
Wai Ting
WT
Lau
Tze Kin
TK
Rogers
Michael S
MS
Leung
Tse Ngong
TN
D017209:Apoptosis; D016207:Cytokines / Q000097:blood; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007150:Immunohistochemistry; D037102:Lectins / Q000097:blood / Q000378:metabolism*; D008297:Male; D010920:Placenta / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000276:immunology*; D011247:Pregnancy; D011485:Protein Binding; D040901:Proteomics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014327:Trophoblasts / Q000378:metabolism; D000097604:Ficolins
D016207:Cytokines; D037102:Lectins; D000097604:Ficolins