MASP-1 Increases Endothelial Permeability
Autor: | Péter Gál, János Rigó, András Masszi, Fruzsina R. Walter, Erika Kajdácsi, László Cervenak, Mária A. Deli, Veronika Makó, Márta L. Debreczeni, Gábor Pál, Zoltán Doleschall, József Dobó, Zsuzsanna Németh, Endre Schwaner |
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Rok vydání: | 2019 |
Předmět: |
lcsh:Immunologic diseases. Allergy
0301 basic medicine Myosin light-chain kinase Immunology PAR-1 Vascular permeability C1-inhibitor Umbilical vein Permeability 03 medical and health sciences 0302 clinical medicine Immune system transcriptome analysis Human Umbilical Vein Endothelial Cells Immunology and Allergy Humans Receptor PAR-1 Cells Cultured Original Research rho-Associated Kinases biology Chemistry angioedema MASP-1 Extravasation Recombinant Proteins Complement system Cell biology Endothelial stem cell 030104 developmental biology Mannose-Binding Protein-Associated Serine Proteases biology.protein endothelial cell lcsh:RC581-607 030215 immunology XPerT assay |
Zdroj: | Frontiers in Immunology Frontiers in Immunology, Vol 10 (2019) |
Popis: | Pathologically increased vascular permeability is an important dysfunction in the pathomechanism of life-threatening conditions, such as sepsis, ischemia/reperfusion, or hereditary angioedema (HAE), diseases accompanied by uncontrolled activation of the complement system. HAE for example is caused by the deficiency of C1-inhibitor (the main regulator of early complement activation), which leads to edematous attacks threatening with circulatory collapse. We have previously reported that endothelial cells become activated during HAE attacks. A natural target of C1-inhibitor is mannan-binding lectin-associated serine protease-1 (MASP-1), a multifunctional serine protease, which plays a key role in the activation of complement lectin pathway. We have previously shown that MASP-1 induces the pro-inflammatory activation of endothelial cells and in this study we investigated whether MASP-1 can directly affect endothelial permeability. All experiments were performed on human umbilical vein endothelial cells (HUVECs). Real-time micro electric sensing revealed that MASP-1 decreases the impedance of HUVEC monolayers and in a recently developed permeability test (XperT), MASP-1 dose-dependently increased endothelial paracellular transport. We show that protease activated receptor-1 mediated intracellular Ca2+-mobilization, Rho-kinase activation dependent myosin light chain (MLC) phosphorylation, cytoskeletal actin rearrangement, and disruption of interendothelial junctions are underlying this phenomenon. Furthermore, in a whole-transcriptome microarray analysis MASP-1 significantly changed the expression of 25 permeability-related genes in HUVECs—for example it up-regulated bradykinin B2 receptor expression. According to our results, MASP-1 has potent permeability increasing effects. During infections or injuries MASP-1 may help eliminate the microbes and/or tissue debris by enhancing the extravasation of soluble and cellular components of the immune system, however, it may also play a role in the pathomechanism of diseases, where edema formation and complement lectin pathway activation are simultaneously present. Our findings also raise the possibility that MASP-1 may be a promising target of anti-edema drug development. |
Databáze: | OpenAIRE |
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