MASP-1 Increases Endothelial Permeability

Márta L. Debreczeni, Zsuzsanna Németh, Erika Kajdácsi, Endre Schwaner, Veronika Makó, András Masszi, Zoltán Doleschall, J. Rigó, Fruzsina R. Walter, Mária A. Deli, G. Pál, J. Dobó, P. Gál, L. Cervenák

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Number of pages1
JournalFrontiers in immunology
Volume10
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Mannose-Binding Protein-Associated Serine Proteases
Permeability
Hereditary Angioedemas
Human Umbilical Vein Endothelial Cells
Mannose-Binding Lectin Complement Pathway
Complement Activation
Edema
Endothelial Cells
PAR-1 Receptor
Bradykinin B2 Receptors
rho-Associated Kinases
Myosin Light Chains
Inborn Genetic Diseases
Capillary Permeability
Serine Proteases
Gene Expression Profiling
Microarray Analysis
Electric Impedance
Reperfusion
Actins

Keywords

  • angioedema
  • C1-inhibitor
  • endothelial cell
  • MASP-1
  • PAR-1
  • permeability
  • transcriptome analysis
  • XPerT assay

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Debreczeni, M. L., Németh, Z., Kajdácsi, E., Schwaner, E., Makó, V., Masszi, A., ... Cervenák, L. (2019). MASP-1 Increases Endothelial Permeability. Frontiers in immunology, 10. https://doi.org/10.3389/fimmu.2019.00991

MASP-1 Increases Endothelial Permeability. / Debreczeni, Márta L.; Németh, Zsuzsanna; Kajdácsi, Erika; Schwaner, Endre; Makó, Veronika; Masszi, András; Doleschall, Zoltán; Rigó, J.; Walter, Fruzsina R.; Deli, Mária A.; Pál, G.; Dobó, J.; Gál, P.; Cervenák, L.

In: Frontiers in immunology, Vol. 10, 01.01.2019.

Research output: Contribution to journalArticle

Debreczeni, ML, Németh, Z, Kajdácsi, E, Schwaner, E, Makó, V, Masszi, A, Doleschall, Z, Rigó, J, Walter, FR, Deli, MA, Pál, G, Dobó, J, Gál, P & Cervenák, L 2019, 'MASP-1 Increases Endothelial Permeability', Frontiers in immunology, vol. 10. https://doi.org/10.3389/fimmu.2019.00991
Debreczeni ML, Németh Z, Kajdácsi E, Schwaner E, Makó V, Masszi A et al. MASP-1 Increases Endothelial Permeability. Frontiers in immunology. 2019 Jan 1;10. https://doi.org/10.3389/fimmu.2019.00991
Debreczeni, Márta L. ; Németh, Zsuzsanna ; Kajdácsi, Erika ; Schwaner, Endre ; Makó, Veronika ; Masszi, András ; Doleschall, Zoltán ; Rigó, J. ; Walter, Fruzsina R. ; Deli, Mária A. ; Pál, G. ; Dobó, J. ; Gál, P. ; Cervenák, L. / MASP-1 Increases Endothelial Permeability. In: Frontiers in immunology. 2019 ; Vol. 10.
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