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| Item Type: | Article |
|---|---|
| Title: | CD74-downregulation of placental macrophage-trophoblastic interactions in preeclampsia |
| Creators Name: | Przybyl, L., Haase, N., Golic, M., Rugor, J., Solano, M.E., Arck, P.C., Gauster, M., Huppertz, B., Emontzpohl, C., Stoppe, C., Bernhagen, J., Leng, L., Bucala, R., Schulz, H., Heuser, A., Weedon-Fekjær, S., Johnsen, G.M., Peetz, D., Luft, F.C., Staff, A.C., Müller, D.N., Dechend, R. and Herse, F. |
| Abstract: | Rationale: MWe hypothesized that Cluster of differentiation 74 (CD74) downregulation on placental macrophages, leading to altered macrophage-trophoblast interaction, is involved in preeclampsia. Objective: Preeclamptic pregnancies feature hypertension, proteinuria and placental anomalies. Feto-placental macrophages regulate villous trophoblast differentiation during placental development. Disturbance of this well-balanced regulation can lead to pathological pregnancies. Methods and Results: We performed whole genome expression analysis of placental tissue. CD74 was one of the most downregulated genes in placentas from preeclamptic women. By RT-PCR, we confirmed this finding in early onset (<34 gestational week, n=26) and late onset (≥34 gestational week, n=24) samples from preeclamptic women, compared to healthy pregnant controls (n=28). CD74 protein levels were analyzed by Western blot and flow cytometry. We identified placental macrophages to express CD74 by immunofluorescence, flow cytometry and RT-PCR. CD74-positive macrophages were significantly reduced in preeclamptic placentas compared to controls. CD74-silenced macrophages showed that the adhesion molecules ALCAM, ICAM4, and Syndecan-2, as well as macrophage adhesion to trophoblasts were diminished. Naïve and activated macrophages lacking CD74 showed a shift towards a pro-inflammatory signature with an increased secretion of TNF , CCL5, and MCP-1, when co-cultured with trophoblasts compared to control macrophages. Trophoblasts stimulated by these factors express more CYP2J2, sFlt1, TNF and IL-8. CD74-knockout mice showed disturbed placental morphology, reduced junctional zone, smaller placentas and impaired spiral artery remodeling with fetal growth restriction. Conclusions: CD74 downregulation in placental macrophages is present in preeclampsia. CD74 downregulation leads to altered macrophage activation towards a pro-inflammatory signature and a disturbed crosstalk with trophoblasts. |
| Keywords: | CD74, Trophoblast, Preeclampsia/Pregnancy, Macrophage, Immunology, Aninals, Mice |
| Source: | Circulation Research |
| ISSN: | 0009-7330 |
| Publisher: | American Heart Association |
| Volume: | 119 |
| Number: | 1 |
| Page Range: | 55-68 |
| Date: | 24 June 2016 |
| Additional Information: | Copyright © 2016 American Heart Association, Inc. |
| Official Publication: | https://doi.org/10.1161/CIRCRESAHA.116.308304 |
| PubMed: | View item in PubMed |
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