Serum MASP-1 in complex with MBL activates endothelial cells

Márton Megyeri, Péter K. Jani, Erika Kajdácsi, J. Dobó, Endre Schwaner, Balázs Major, J. Rigó, P. Závodszky, Steffen Thiel, L. Cervenák, P. Gál

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The complement system plays an important role in the induction of inflammation. In this study we demonstrate that the initiation complexes of the lectin pathway, consisting of mannose-binding lectin (MBL) and associated serine proteases (MASPs) elicit Ca2+ signaling in cultured endothelial cells (HUVECs). This is in agreement with our previous results showing that the recombinant catalytic fragment of MASP-1 activates endothelial cells by cleaving protease activated receptor 4. Two other proteases, MASP-2 and MASP-3 are also associated with MBL. Earlier we showed that recombinant catalytic fragment of MASP-2 cannot activate HUVECs, and in this study we demonstrate that the same fragment of MASP-3 has also no effect. We find the same to be the case if we use recombinant forms of the N-terminal parts of MASP-1 and MASP-2 which only contain non-enzymatic domains. Moreover, stable zymogen mutant form of MASP-1 was also ineffective to stimulate endothelial cells, which suggests that in vivo MASP-1 have the ability to activate endothelial cells directly as well as to activate the lectin pathway simultaneously. We show that among the components of the MBL-MASPs complexes only MASP-1 is able to trigger response in HUVECs and the proteolytic activity of MASP-1 is essential. Our results strengthen the view that MASP-1 plays a central role in the early innate immune response.

Original languageEnglish
Pages (from-to)39-45
Number of pages7
JournalMolecular Immunology
Volume59
Issue number1
DOIs
Publication statusPublished - May 2014

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Mannose-Binding Protein-Associated Serine Proteases
Mannose-Binding Lectin
Endothelial Cells
Serum
Lectins
Enzyme Precursors
Serine Proteases

Keywords

  • Cell activation
  • Complement lectin pathway
  • Endothelial cell
  • MBL-associated serine proteases
  • Protease activated receptor

ASJC Scopus subject areas

  • Molecular Biology
  • Immunology

Cite this

Serum MASP-1 in complex with MBL activates endothelial cells. / Megyeri, Márton; Jani, Péter K.; Kajdácsi, Erika; Dobó, J.; Schwaner, Endre; Major, Balázs; Rigó, J.; Závodszky, P.; Thiel, Steffen; Cervenák, L.; Gál, P.

In: Molecular Immunology, Vol. 59, No. 1, 05.2014, p. 39-45.

Research output: Contribution to journalArticle

Megyeri, Márton ; Jani, Péter K. ; Kajdácsi, Erika ; Dobó, J. ; Schwaner, Endre ; Major, Balázs ; Rigó, J. ; Závodszky, P. ; Thiel, Steffen ; Cervenák, L. ; Gál, P. / Serum MASP-1 in complex with MBL activates endothelial cells. In: Molecular Immunology. 2014 ; Vol. 59, No. 1. pp. 39-45.
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