Bone morphogenetic protein (BMP)9 is a circulating growth factor that is part of the TGF-b superfamily and is an essential regulator of vascular endothelial homeostasis.

BMP9 upregulates TLR4 expression in human endothelial cells and BMP9 pretreatment synergistically increases human neutrophil recruitment to LPS-stimulated human endothelial monolayers in an in vitro flow adhesion assay. BMP9 alone doesnot induce neutrophil recruitment to the endothelium. E-selectin and VCAM-1, 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 inhibits the BMP9-induced expression of TLR4 and VCAM-1 and inhibits BMP9-induced human neutrophil recruitment to LPS-stimulated human endothelial cells.

BMP9 treatment also increases leukocyte recruitment within the pulmonary circulation in a mouse acute endotoxemia model. 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.