PhD Scientific Days 2017

Oral Presentations: Cardiovascular

The effect of complement MASP-1 on endothelial cell permeability

Előadó neve

Debreczeni, Márta Lídia

Előadó munkahelye

Semmelweis University, 3rd Department of Internal Medicine, Research Laboratory

Előadó telefonszáma

+36304594020

Előadó e-mail címe

martidebreczeni@gmail.com

Az előadás címe

The effect of complement MASP-1 on endothelial cell permeability

Szerző(k) neve és munkahelye

Márta Lídia Debreczeni1, Erika Kajdácsi1, Endre Schwaner1, László Cervenak1
Semmelweis University, 3rd Department of Internal Medicine, Research Laboratory, Budapest

Szekció

Oral Presentations: Cardiovascular

Data of the presenter

Doctoral School: Doctoral School of Basic Medicine
Program: Clinical and Experimental Cardiology / Atherosclerosis
Supervisor: László Cervenak
martidebreczeni@gmail.com

Text of the abstract

Introduction: Hereditary angioedema (HAE) resulting from the deficiency of C1 inhibitor is a rare, but potentially life-threatening disorder, which is characterized by increased endothelial permeability. One of the enzymes blocked by C1-inhibitor, mannan-binding lectin-associated serine protease-1 (MASP-1), is the most important serine protease of the complement lectin pathway. We previously showed that MASP-1 can activate endothelial cells, which raised the question whether MASP-1 can increase endothelial permeability and thus take part in the triggering of the edematous attacks.
Aims: To answer this question it was necessary to develop a new and simple test suitable for permeability measurements. We also aimed to explore the mechanisms by which MASP-1 exerts its cellular effects.
Methods: We used confluent human umbilical vein endothelial cell (HUVEC) culture as a model. We have successfully optimized a new, simple, cheap and high-throughput method for permeability measurements, which is based on the reaction of the biotinylated gelatin on the surface of the cell culture plate and a streptavidin-conjugated fluorescent dye passing between the endothelial cells. Some of the key adhesion molecules and components of the cytoskeleton were visualized by immunofluorescence microscopy.
Results: In the permeability tests, MASP-1 could significantly and dose-dependently increase the rate of endothelial paracellular transport, which effect was completely blocked by C1-inhibitor. Using proteinase activated receptor (PAR) antagonists we demonstrated that the permeability increasing effect of MASP-1 is mediated mostly by PAR-1. We also showed that MASP-1 induces cytoskeletal actin rearrangement by the phosphorylation of myosin light chains, which was dependent on p160 ROCK activity.
We supported our findings by visualization of key adhesion molecules. In these tests, MASP-1 changed the molecular pattern of PECAM-1, VE-cadherin and ZO-1, and increased the size of inter-endothelial gaps.
Conclusion: Our findings raise the possibility that MASP-1 could play an important role in the pathomechanism of HAE.

Kind

Szabad

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

1289

Authors (legacy)

Márta Lídia Debreczeni1, Erika Kajdácsi1, Endre Schwaner1, László Cervenak1
Semmelweis University, 3rd Department of Internal Medicine, Research Laboratory, Budapest