PhD Scientific Days 2019

Poster presentations: Cardio-vascular sciences

LPS and endogenous factors synergistically regulate endothelial permeability

Előadó neve

Ms. Németh, Zsuzsanna

Előadó munkahelye

3rd Department of Internal Medicine, Semmelweis University, Budapest

Előadó telefonszáma

06204207589

Előadó e-mail címe

nemethzsanna@gmail.com

Az előadás címe

LPS and endogenous factors synergistically regulate endothelial permeability

Szerző(k) neve és munkahelye

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

Bemutatás módja

Poszter

Szekció

Poster presentations: Cardio-vascular sciences

Language of the presentation

English

Témacsoport

cardio-vascular sciences

Összefoglaló szövege

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.

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4152

Presentation file URL

//docs.kmcongress.com/phd2019/eposter_6028.png

Authors (legacy)

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

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