Neutrophils engage the kallikrein-kinin system to open up the endothelial barrier in acute inflammation


Publication type
Article
Appears in Collections:
Metrics
Abstract
Neutrophil recruitment and plasma exudation are key elements in the immune response to injury or infection. Activated neutrophils stimulate opening of the endothelial barrier; however, the underlying mechanisms have remained largely unknown. In this study, we identified a pivotal role of the proinflammatory kallikrein-kinin system and consequent formation of bradykinin in neutrophil-evoked vascular leak. In mouse and hamster models of acute inflammation, inhibitors of bradykinin generation, and signaling markedly reduced plasma exudation in response to chemoattractant activation of neutrophils. The neutrophil-driven leak was likewise suppressed in mice deficient in either the bradykinin B-2 receptor or factor XII (initiator of the kallikrein-kinin system). In human endothelial cell monolayers, material secreted from activated neutrophils induced cytoskeletal rearrangement, leading to paracellular gap formation in a bradykinin-dependent manner. As a mechanistic basis, we found that a neutrophil-derived heparin-binding protein (HBP/azurocidin) displaced the bradykinin precursor high-molecular-weight kininogen from endothelial cells, thereby enabling proteolytic processing of kininogen into bradykinin by neutrophil and plasma proteases. These data provide novel insight into the signaling pathway by which neutrophils open up the endothelial barrier and identify the kallikrein-kinin system as a target for therapeutic interventions in acute inflammatory reactions.Kenne, E., Rasmuson, J., Renne, T., Vieira, M. L., Muller-Esterl, W., Herwald, H., Lindbom, L. Neutrophils engage the kallikrein-kinin system to open up the endothelial barrier in acute inflammation.
Reference
Kenne E, Rasmuson J, Renné T, Vieira ML, Müller-Esterl W, Herwald H, et al. Neutrophils engage the kallikrein-kinin system to open up the endothelial barrier in acute inflammation. FASEB J. 2019 Jan;33(2):2599-2609. doi:10.1096/fj.201801329R.
Link to cite this reference
https://repositorio.butantan.gov.br/handle/butantan/2666
Journal title
Issue Date
2019


Files in This Item:

Existing users please Login
10.1096fj.201801329R.pdf
Size: 1.9 MB
Format: Adobe PDF
Embargoed until January 1, 2999    Request a copy
Show full item record

The access to the publications deposited in this repository respects the licenses from journals and publishers.