Bone morphogenetic protein 9 enhances lipopolysaccharide-induced leukocyte recruitment to the vascular endothelium
Author(s)
Type
Journal Article
Abstract
Bone morphogenetic protein (BMP)9 is a circulating growth factor that is part of the TGF-β superfamily and is an essential regulator of vascular endothelial homeostasis. Previous studies have suggested a role for BMP9 signaling in leukocyte recruitment to the endothelium, but the directionality of this effect and underlying mechanisms have not been elucidated. In this study, we report that BMP9 upregulates TLR4 expression in human endothelial cells and that BMP9 pretreatment synergistically increases human neutrophil recruitment to LPS-stimulated human endothelial monolayers in an in vitro flow adhesion assay. BMP9 alone did not induce neutrophil recruitment to the endothelium. We also show that E-selectin and VCAM-1, but not ICAM-1, are upregulated in response to BMP9 in LPS-stimulated human endothelial cells. Small interfering RNA knockdown of activin receptor–like kinase 1 inhibited the BMP9-induced expression of TLR4 and VCAM-1 and inhibited BMP9-induced human neutrophil recruitment to LPS-stimulated human endothelial cells. BMP9 treatment also increased leukocyte recruitment within the pulmonary circulation in a mouse acute endotoxemia model. These results demonstrate that although BMP9 alone does not influence leukocyte recruitment, it primes the vascular endothelium to mount a more intense response when challenged with LPS through an increase in TLR4, E-selectin, and VCAM-1 and ultimately through enhanced leukocyte recruitment.
Date Issued
2016-10-15
Date Acceptance
2016-08-18
Citation
Journal of Immunology, 2016, 197 (8), pp.3302-3314
ISSN
1550-6606
Publisher
American Association of Immunologists
Start Page
3302
End Page
3314
Journal / Book Title
Journal of Immunology
Volume
197
Issue
8
Copyright Statement
© 2016 by The American Association of Immunologists, Inc.
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000387965100032&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Immunology
HEREDITARY HEMORRHAGIC TELANGIECTASIA
ACUTE LUNG INJURY
CELL-ADHESION MOLECULE-1
RECEPTOR-LIKE KINASE-1
TOLL-LIKE RECEPTOR-4
SIGNALING PATHWAYS
HUMAN NEUTROPHILS
TGF-BETA
PSEUDOMONAS-AERUGINOSA
BMPR-II
Publication Status
Published
Date Publish Online
2016-10-07