Complement protease MASP-1 activates human endothelial cells: PAR4 activation is a link between complement and endothelial function

Márton Megyeri, Veronika Makó, László Beinrohr, Zoltán Doleschall, Z. Prohászka, L. Cervenák, P. Závodszky, P. Gál

Research output: Contribution to journalArticle

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Abstract

Activation of the complement system can induce and enhance inflammatory reaction. Mannose-binding lectin-associated serine protease-1 (MASP-1) is an abundant protease of the complement lectin pathway; however, its physiological function is unclear. In this study, we demonstrate for the first time that MASP-1 is able to activate Ca2+ signaling, NF-κB, and p38 MAPK pathways in cultured HUVECs. Activation was initiated by MASP-1 only; the related protease, MASP-2, had no such effect. The phenomenon was dependent on the proteolytic activity of MASP-1, suggesting modulation of endothelial cell function through a proteaseactivated receptor (PAR). Using synthetic peptide substrates representing the protease-sensitive regions of PARs, we were able to demonstrate that PAR4 is a target of MASP-1. The presence of functionally active PAR4 in HUVECs was demonstrated using PAR4 agonist peptide and mRNA quantification. Finally, we showed that the amount of membrane-bound intact PAR4 decreases after MASP-1 treatment. All of these results provide a novel link between the regulation of endothelial cell function and complement system activation, and they suggest that MASP-1-induced PAR4 activation could contribute to the development of the inflammatory reaction.

Original languageEnglish
Pages (from-to)3409-3416
Number of pages8
JournalJournal of Immunology
Volume183
Issue number5
DOIs
Publication statusPublished - Sep 1 2009

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Mannose-Binding Lectin
Serine Proteases
Peptide Hydrolases
Endothelial Cells
Complement Activation
Mannose-Binding Protein-Associated Serine Proteases
Mannose-Binding Lectin Complement Pathway
Peptides
p38 Mitogen-Activated Protein Kinases
human PRSS1 protein
Messenger RNA
Membranes

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Complement protease MASP-1 activates human endothelial cells : PAR4 activation is a link between complement and endothelial function. / Megyeri, Márton; Makó, Veronika; Beinrohr, László; Doleschall, Zoltán; Prohászka, Z.; Cervenák, L.; Závodszky, P.; Gál, P.

In: Journal of Immunology, Vol. 183, No. 5, 01.09.2009, p. 3409-3416.

Research output: Contribution to journalArticle

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AU - Doleschall, Zoltán

AU - Prohászka, Z.

AU - Cervenák, L.

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