Bone morphogenetic protein 9 enhances lipopolysaccharide-induced leukocyte recruitment to the vascular endothelium

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Bone morphogenetic protein 9 enhances lipopolysaccharide-induced leukocyte recruitment to the vascular endothelium. / Appleby, Sarah L; Mitrofan, Claudia-Gabriela; Crosby, Alexi; Hoenderdos, Kim; Lodge, Katharine; Upton, Paul D; Yates, Clara M; Nash, Gerard B; Chilvers, Edwin R; Morrell, Nicholas W.

In: Journal of Immunology, Vol. 197, 19.09.2016.

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Appleby, Sarah L ; Mitrofan, Claudia-Gabriela ; Crosby, Alexi ; Hoenderdos, Kim ; Lodge, Katharine ; Upton, Paul D ; Yates, Clara M ; Nash, Gerard B ; Chilvers, Edwin R ; Morrell, Nicholas W. / Bone morphogenetic protein 9 enhances lipopolysaccharide-induced leukocyte recruitment to the vascular endothelium. In: Journal of Immunology. 2016 ; Vol. 197.

Bibtex

@article{d379303926a94fc8b7600d342a42bdc6,
title = "Bone morphogenetic protein 9 enhances lipopolysaccharide-induced leukocyte recruitment to the vascular endothelium",
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.",
author = "Appleby, {Sarah L} and Claudia-Gabriela Mitrofan and Alexi Crosby and Kim Hoenderdos and Katharine Lodge and Upton, {Paul D} and Yates, {Clara M} and Nash, {Gerard B} and Chilvers, {Edwin R} and Morrell, {Nicholas W}",
note = "Copyright {\textcopyright} 2016 by The American Association of Immunologists, Inc.",
year = "2016",
month = sep,
day = "19",
doi = "10.4049/​jimmunol.1601219",
language = "English",
volume = "197",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",

}

RIS

TY - JOUR

T1 - Bone morphogenetic protein 9 enhances lipopolysaccharide-induced leukocyte recruitment to the vascular endothelium

AU - Appleby, Sarah L

AU - Mitrofan, Claudia-Gabriela

AU - Crosby, Alexi

AU - Hoenderdos, Kim

AU - Lodge, Katharine

AU - Upton, Paul D

AU - Yates, Clara M

AU - Nash, Gerard B

AU - Chilvers, Edwin R

AU - Morrell, Nicholas W

N1 - Copyright © 2016 by The American Association of Immunologists, Inc.

PY - 2016/9/19

Y1 - 2016/9/19

N2 - 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.

AB - 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.

U2 - 10.4049/​jimmunol.1601219

DO - 10.4049/​jimmunol.1601219

M3 - Article

C2 - 27647829

VL - 197

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

ER -