Unknown,Transcriptomics,Genomics,Proteomics

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Endothelial Cells Provide an Instructive Niche for the Differentiation and Functional Polarization of M2-like Macrophages

ABSTRACT: Endothelial cells and macrophages are known to engage in tight and specific interactions that contribute to the modulation of vascular function. Here we show that adult endothelial cells provide critical signals for the selective growth and differentiation of macrophages from several types of hematopoietic progenitor cells. The process features the formation of well-organized colonies that exhibit progressive differentiation from the center to the periphery and towards an M2-like phenotype, characterized by enhanced expression of Tie2 and CD206/Mrc1. These colonies are long-lived as long as the contact with the endothelium is maintained; removal of the endothelial monolayer results in rapid dissolution of the macrophage colonies. Not only the maintenance but also the formation of the colonies is strictly dependent on endothelial contact. We further found that M-CSF produced by the endothelium is critical for the expansion of the macrophage colonies and that blockade of M-CSF receptor impairs colony growth. Functional analyses indicate that these macrophages are capable of accelerating angiogenesis, promoting tumor growth and effectively engaging in tight associations with endothelial cells in vivo. These findings uncover a critical role of endothelial cells in the induction of macrophage differentiation and their ability to promote further polarization towards a proangiogenic phenotype. 8 samples were sequenced: bone marrow derived macrophages (BMDM) were stimulated with LPS, IL4, or none. Colony cells induced by endothelial cells for 7 days. Each was duplicated.

ORGANISM(S): Mus musculus

SUBMITTER: Calvin Pan

PROVIDER: E-GEOD-39660 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Chen2006 - Nitric Oxide Release from Endothelial Cells This model is described in the article: Theoretical analysis of biochemical pathways of nitric oxide release from vascular endothelial cells. Chen K, Popel AS. Free Radic. Biol. Med. 2006 Aug; 41(4): 668-680 Abstract: Vascular endothelium expressing endothelial nitric oxide synthase (eNOS) produces nitric oxide (NO), which has a number of important physiological functions in the microvasculature. The rate of NO production by the endothelium is a critical determinant of NO distribution in the vascular wall. We have analyzed the biochemical pathways of NO synthesis and formulated a model to estimate NO production by the microvascular endothelium under physiological conditions. The model quantifies the NO produced by eNOS based on the kinetics of NO synthesis and the availability of eNOS and its intracellular substrates. The predicted NO production from microvessels was in the range of 0.005-0.1 microM/s. This range of predicted values is in agreement with some experimental values but is much lower than other rates previously measured or estimated from experimental data with the help of mathematical modeling. Paradoxical discrepancies between the model predictions and previously reported results based on experimental measurements of NO concentration in the vicinity of the arteriolar wall suggest that NO can also be released through eNOS-independent mechanisms, such as catalysis by neuronal NOS (nNOS). We also used our model to test the sensitivity of NO production to substrate availability, eNOS concentration, and potential rate-limiting factors. The results indicated that the predicted low level of NO production can be attributed primarily to a low expression of eNOS in the microvascular endothelial cells. This model is hosted on BioModels Database and identified by: BIOMD0000000676. To cite BioModels Database, please use: Chelliah V et al. BioModels: ten-year anniversary. Nucl. Acids Res. 2015, 43(Database issue):D542-8. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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Endothelial Cells Provide an Instructive Niche for the Differentiation and Functional Polarization of M2-like Macrophages

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