PhD Scientific Days 2019

Budapest, April 25–26, 2019

LPS and endogenous factors synergistically regulate endothelial permeability

Németh, Zsuzsanna

Zsuzsanna Németh1, Márta L. Debreczeni1, József Dobó2, Péter Gál2, László Cervenak1

1 3rd Department of Internal Medicine, Semmelweis University, Budapest
2 Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest

Language of the presentation

English

Text of the abstract

Activation of the endothelium towards an increased vascular permeability can lead to the development of severe, life-threatening edematous attacks, for example in the case of hereditary angioedema (HAE) or sepsis. Both exogenous (e.g. bacterial LPS) and endogenous (e.g. complement factors) inflammatory components play a role in the pathomechanism of these diseases. Therefore, we wanted to investigate how these various components (mannan-binding lectin-associated serine protease 1 – MASP-1, histamine, bradykinin and LPS) can interact with one another to influence endothelial cell permeability.

In our earlier studies, we showed that MASP-1 can directly increase endothelial permeability and activate the expression of permeability related genes, including the B2 bradykinin receptor (BDKRB2). We measured the mRNA level of BDKRB1 and 2 with qPCR and found that MASP-1 up-regulated the level of BDKRB2, while LPS increased the expression of both bradykinin receptors. In concert with this, the MASP-1 or LPS pretreated cells showed significantly greater Ca2+-mobilization to bradykinin than those that were not pretreated (measured with fluorescence microscopy).
LPS also induced the mRNA level of HRH1 and PAR2, which are receptors of histamine and MASP-1, respectively, on endothelial cells. Furthermore, we demonstrated that these factors elicited greater Ca2+-mobilization after LPS pretreatment.
To measure the endothelial permeability, we used the modified X-per-T method. The LPS pretreatment could significantly increase endothelial permeability in response to MASP-1.

Our findings highlight that significant interaction can occur amongst endothelial cell activators (between LPS and MASP-1, LPS and bradykinin, LPS and histamine, and MASP-1 and bradykinin) in the regulation of endothelial cell permeability. These synergistic interactions may give us a more detailed picture on the pathogenesis of HAE and sepsis, as well as on their potential therapeutic approaches.

Data of the presenter

Doctoral School: Basic and Translational Medicine
Program: Vascular Pathophysiology / Atherosclerosis
Supervisor: László Cervenak
E-mail address: nemethzsanna@gmail.com
poster presentation