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CD74-Downregulation of Placental Macrophage-Trophoblastic Interactions in Preeclampsia

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CD74-Downregulation of Placental Macrophage-Trophoblastic Interactions in Preeclampsia. / Przybyl, Lukasz; Haase, Nadine; Golic, Michaela; Rugor, Julianna; Solano, Maria E; Arck, Petra C; Gauster, Martin; Huppertz, Berthold; Emontzpohl, Christoph; Stoppe, Christian; Bernhagen, Juergen; Leng, Lin; Bucala, Richard; Schulz, Herbert; Heuser, Arnd; Weedon-Fekjaer, Susanne; Johnsen, Guro M; Peetz, Dirk; Luft, Friedrich C; Staff, Anne Cathrine; Mueller, Dominik N; Dechend, Ralf; Herse, Florian.

In: CIRC RES, Vol. 119, No. 1, 19.05.2016, p. 55-68.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Przybyl, L, Haase, N, Golic, M, Rugor, J, Solano, ME, Arck, PC, Gauster, M, Huppertz, B, Emontzpohl, C, Stoppe, C, Bernhagen, J, Leng, L, Bucala, R, Schulz, H, Heuser, A, Weedon-Fekjaer, S, Johnsen, GM, Peetz, D, Luft, FC, Staff, AC, Mueller, DN, Dechend, R & Herse, F 2016, 'CD74-Downregulation of Placental Macrophage-Trophoblastic Interactions in Preeclampsia', CIRC RES, vol. 119, no. 1, pp. 55-68. https://doi.org/10.1161/CIRCRESAHA.116.308304

APA

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-Fekjaer, S., Johnsen, G. M., Peetz, D., Luft, F. C., ... Herse, F. (2016). CD74-Downregulation of Placental Macrophage-Trophoblastic Interactions in Preeclampsia. CIRC RES, 119(1), 55-68. https://doi.org/10.1161/CIRCRESAHA.116.308304

Vancouver

Przybyl L, Haase N, Golic M, Rugor J, Solano ME, Arck PC et al. CD74-Downregulation of Placental Macrophage-Trophoblastic Interactions in Preeclampsia. CIRC RES. 2016 May 19;119(1):55-68. https://doi.org/10.1161/CIRCRESAHA.116.308304

Bibtex

@article{cccefc57dc3d435abb60192dd6859322,
title = "CD74-Downregulation of Placental Macrophage-Trophoblastic Interactions in Preeclampsia",
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. Na{\"i}ve 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.",
author = "Lukasz Przybyl and Nadine Haase and Michaela Golic and Julianna Rugor and Solano, {Maria E} and Arck, {Petra C} and Martin Gauster and Berthold Huppertz and Christoph Emontzpohl and Christian Stoppe and Juergen Bernhagen and Lin Leng and Richard Bucala and Herbert Schulz and Arnd Heuser and Susanne Weedon-Fekjaer and Johnsen, {Guro M} and Dirk Peetz and Luft, {Friedrich C} and Staff, {Anne Cathrine} and Mueller, {Dominik N} and Ralf Dechend and Florian Herse",
year = "2016",
month = may,
day = "19",
doi = "10.1161/CIRCRESAHA.116.308304",
language = "English",
volume = "119",
pages = "55--68",
journal = "CIRC RES",
issn = "0009-7330",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

RIS

TY - JOUR

T1 - CD74-Downregulation of Placental Macrophage-Trophoblastic Interactions in Preeclampsia

AU - Przybyl, Lukasz

AU - Haase, Nadine

AU - Golic, Michaela

AU - Rugor, Julianna

AU - Solano, Maria E

AU - Arck, Petra C

AU - Gauster, Martin

AU - Huppertz, Berthold

AU - Emontzpohl, Christoph

AU - Stoppe, Christian

AU - Bernhagen, Juergen

AU - Leng, Lin

AU - Bucala, Richard

AU - Schulz, Herbert

AU - Heuser, Arnd

AU - Weedon-Fekjaer, Susanne

AU - Johnsen, Guro M

AU - Peetz, Dirk

AU - Luft, Friedrich C

AU - Staff, Anne Cathrine

AU - Mueller, Dominik N

AU - Dechend, Ralf

AU - Herse, Florian

PY - 2016/5/19

Y1 - 2016/5/19

N2 - 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.

AB - 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.

U2 - 10.1161/CIRCRESAHA.116.308304

DO - 10.1161/CIRCRESAHA.116.308304

M3 - SCORING: Journal article

C2 - 27199465

VL - 119

SP - 55

EP - 68

JO - CIRC RES

JF - CIRC RES

SN - 0009-7330

IS - 1

ER -