Coordinated expression of TNFα- and VEGF-mediated signaling components by placental macrophages in early and late pregnancy

O V Pavlov; D A Niauri; A V Selutin; S A Selkov

doi:10.1016/j.placenta.2016.04.008

Coordinated expression of TNFα- and VEGF-mediated signaling components by placental macrophages in early and late pregnancy

Placenta. 2016 Jun:42:28-36. doi: 10.1016/j.placenta.2016.04.008. Epub 2016 Apr 7.

Authors

O V Pavlov¹, D A Niauri², A V Selutin³, S A Selkov³

Affiliations

¹ Laboratory of Immunology, D.O.Ott Research Institute for Obstetrics, Gynecology and Reproduction, 3 Mendeleev Line, 199034 St. Petersburg, Russia. Electronic address: ovpavlov@hotmail.com.
² Department of Obstetrics, Gynecology and Reproduction, St. Petersburg State University, 7-9 University Embankment, 199034 St. Petersburg, Russia.
³ Laboratory of Immunology, D.O.Ott Research Institute for Obstetrics, Gynecology and Reproduction, 3 Mendeleev Line, 199034 St. Petersburg, Russia.

PMID: 27238711
DOI: 10.1016/j.placenta.2016.04.008

Abstract

Introduction: Mononuclear phagocytes are thought to significantly contribute to cytokine regulation at the maternal-foetal interface, but the role of placental macrophages has been poorly investigated. TNFα and VEGF were demonstrated to have regulatory effects on basic structures of the placenta, particularly the trophoblast and blood vessels. The aims of this study were to determine the expression of TNFα, VEGF and related receptors in placental macrophages, and how does the participation of placental macrophages alter with gestational age in TNFα- and VEGF-mediated signaling.

Methods: Macrophages were isolated from placental villous tissue from normal pregnancies at either 9-12 or 38-40 weeks gestation. Cell surface receptors (TNFR1, TNFR2, VEGFR1, and VEGFR2) and intracellular TNFα and VEGF were quantified by flow cytometry after antibody staining. Basal and stimulated secretion of both cytokines and soluble TNF receptors was quantified by cytometric bead arrays. Secreted VEGFR1 was measured by ELISA.

Results: The expression of TNFR1 and VEGFR1 was remarkably variable and did not change from first to third trimester. There was minimal basal TNFα production in the placental macrophages, but nearly all cells in the population produced VEGF. TNFα and VEGF secretion increased with gestational age accompanied by decreased secretion of the antagonists sTNFR1 and sVEGFR. Macrophages isolated from early term placentas were less effective in responding to bacterial endotoxin. Lipopolysaccharide induced increases in the secretion of TNFα, TNFR1, TNFR2, and VEGFR1 but did not affect the production of VEGF. In late pregnancy, a significant correlation was observed between TNFR1 and VEGFR1.

Discussion: The progression of pregnancy is accompanied by the concerted increase in TNFα and VEGF secretion and decrease in the production of their soluble receptors, but the expression of cell surface receptors does not depend on gestational age. The observed patterns of basal and stimulated expression of TNFα and VEGF may reflect the dual immune and morphogenetic roles of placental macrophages in gestation. Compatible patterns of TNFR1 and VEGFR1 expression suggest common regulatory pathways for these receptors.

Keywords: Placental macrophages; TNFR1; TNFα; VEGF; VEGFR1.

MeSH terms

Adult
Female
Humans
Lipopolysaccharides / pharmacology
Macrophages / drug effects
Macrophages / metabolism*
Placenta / drug effects
Placenta / metabolism*
Pregnancy
Pregnancy Trimester, First
Pregnancy Trimester, Third
Receptors, Tumor Necrosis Factor / metabolism*
Receptors, Vascular Endothelial Growth Factor / metabolism*
Signal Transduction / drug effects
Signal Transduction / physiology*
Tumor Necrosis Factor-alpha / metabolism
Vascular Endothelial Growth Factor A / metabolism
Young Adult

Substances

Lipopolysaccharides
Receptors, Tumor Necrosis Factor
Tumor Necrosis Factor-alpha
Vascular Endothelial Growth Factor A
Receptors, Vascular Endothelial Growth Factor