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VEGF may contribute to macrophage recruitment and M2 polarization in the decidua.
Wheeler, Karen C; Jena, Manoj K; Pradhan, Bhola S; Nayak, Neha; Das, Subhendu; Hsu, Chaur-Dong; Wheeler, David S; Chen, Kang; Nayak, Nihar R.
Afiliación
  • Wheeler KC; Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan, United States of America.
  • Jena MK; Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan, United States of America.
  • Pradhan BS; Department of Biotechnology, School of Bioengineering and Biosciences, Lovely Professional University (LPU), Phagwara, Punjab, India.
  • Nayak N; Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan, United States of America.
  • Das S; Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan, United States of America.
  • Hsu CD; Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan, United States of America.
  • Wheeler DS; Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan, United States of America.
  • Chen K; Division of Pulmonary and Critical Care Medicine, University of Michigan Health System, Ann Arbor, Michigan, United States of America.
  • Nayak NR; Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan, United States of America.
PLoS One ; 13(1): e0191040, 2018.
Article en En | MEDLINE | ID: mdl-29324807
It is increasingly evident that cytokines and growth factors produced in the decidua play a pivotal role in the regulation of the local immune microenvironment and the establishment of pregnancy. One of the major growth factors produced in the decidua is vascular endothelial growth factor (VEGF), which acts not only on endothelial cells, but also on multiple other cell types, including macrophages. We sought to determine whether decidua-derived VEGF affects macrophage recruitment and polarization using human endometrial/decidual tissue samples, primary human endometrial stromal cells (ESCs), and the human monocyte cell line THP1. In situ hybridization was used for assessment of local VEGF expression and immunohistochemistry was used for identification and localization of CD68-positive endometrial macrophages. Macrophage migration in culture was assessed using a transwell migration assay, and the various M1/M2 phenotypic markers and VEGF expression were assessed using quantitative real-time PCR (qRT-PCR). We found dramatic increases in both VEGF levels and macrophage numbers in the decidua during early pregnancy compared to the secretory phase endometrium (non-pregnant), with a significant increase in M2 macrophage markers, suggesting that M2 is the predominant macrophage phenotype in the decidua. However, decidual samples from preeclamptic pregnancies showed a significant shift in macrophage phenotype markers, with upregulation of M1 and downregulation of M2 markers. In THP1 cultures, VEGF treatment significantly enhanced macrophage migration and induced M1 macrophages to shift to an M2 phenotype. Moreover, treatment with conditioned media from decidualized ESCs induced changes in macrophage migration and polarization similar to that of VEGF treatment. These effects were abrogated by the addition of a potent VEGF inhibitor. Together these results suggest that decidual VEGF plays a significant role in macrophage recruitment and M2 polarization, and that inhibition of VEGF signaling may contribute to the shift in macrophage polarity observed in different pregnancy disorders, including preeclampsia.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Polaridad Celular / Decidua / Factor A de Crecimiento Endotelial Vascular / Macrófagos Tipo de estudio: Prognostic_studies Límite: Adult / Female / Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Polaridad Celular / Decidua / Factor A de Crecimiento Endotelial Vascular / Macrófagos Tipo de estudio: Prognostic_studies Límite: Adult / Female / Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos