The Endothelial Protective Factors, BMP9 and BMP10, Inhibit CCL2 Release By Human Vascular Endothelial Cells
De Souza, Patricia
Journal of Cell Science
The Company of Biologists Ltd.
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Upton, P., Park, J., De Souza, P., Davies, R., Griffiths, M., Wort, S., & Morrell, N. The Endothelial Protective Factors, BMP9 and BMP10, Inhibit CCL2 Release By Human Vascular Endothelial Cells. Journal of Cell Science https://doi.org/10.17863/CAM.53806
Bone morphogenetic protein (BMP)-9 and BMP10 are circulating ligands that mediate endothelial cell (EC) protection via complexes of the type I receptor, ALK1, and the type II receptors, the activin type-IIA and bone morphogenetic type II receptors. We previously demonstrated that BMP9 induces the expression of interleukin-6, interleukin-8 and E-selectin in ECs and may influence their interactions with monocytes and neutrophils. We asked whether BMP9 and BMP10 regulate the expression of Chemokine (C-C motif) ligand 2 (CCL2), a key chemokine involved in monocyte-macrophage chemoattraction. Here, we show that BMP9 and BMP10 repress basal CCL2 expression and release from human pulmonary artery ECs and aortic ECs. This was dependent on ALK1 and co-dependent on ACTR-IIA and BMPR-II. Assessment of canonical Smad signalling indicated a reliance of this response on Smad4. Of note, Smad1/5 signalling contributed only at BMP9 concentrations similar to those in the circulation. In the context of inflammation, BMP9 did not alter the induction of CCL2 by TNF-α. As CCL2 promotes monocyte/macrophage chemotaxis and endothelial permeability, these data support the concept that BMP9 preserves basal endothelial integrity.
Rachel J Davies was a PhD student working in the Department of Medicine and supervised by Professor NW Morrell when she undertook work reported in this manuscript. She was funded by a Wellcome Trust Clinical Research Training Fellowship (Grant Number: GR077167MA)
British Heart Foundation (RG/13/4/30107)
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This record's DOI: https://doi.org/10.17863/CAM.53806
This record's URL: https://www.repository.cam.ac.uk/handle/1810/306718
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