Cooperative effects of MASP-1 and other activating signals on endothelial cell behavior
Horváthné Németh Zsuzsanna
Theoretical and Translational Medicine
Dr. Kellermayer Miklós
Belgyógyászati és Hematológiai Klinika, könyvtár
2025-01-27 11:00:00
Vascular Pathophysiology / Atherosclerosis
Dr. Prohászka Zoltán
Dr. Cervenak László
Dr. Futosi Krisztina
Dr. Cserepes Mihály
Dr. Kellermayer Miklós
Dr. Hegyesi Hargita
Dr. Espárné Schneider Andrea
Endothelial cells (ECs) constitute the innermost layer of the vessel walls. They act as
signal integrators, creating the adequate respond to the various molecules present in the
blood and play a crucial role in wound healing processes after injury. MASP-1, the most
abundant enzyme of complement lectin pathway induces a proinflammatory phenotype
in ECs and its activation is triggered by different pathogens or altered host cells. An
inflammatory response is also an integral part of the wound healing process, and the
participation of the complement lectin pathway is an actively researched topic.
Our aim was to investigate the combined effect of MASP-1 and different activating
factors (LPS, histamine, bradykinin and IFNγ) in the induction of proinflammatory
phenotype in ECs. We also studied the cellular effect of mechanical wounding in the
presence or absence of MASP-1, as an evident model for proinflammatory activation.
We demonstrated that MASP-1 cooperated with all the above-mentioned activating
factors in a variety of ways. LPS pretreatment increased the expression of PAR-2, a
MASP-1 receptor, and furthermore, MASP-1 and LPS enhanced each other’s effects in
regulating IL-8, E-selectin, Ca2+-mobilization, and changes in permeability. We showed
that cotreatment of MASP-1 and IFNγ increased the IL-8 expression of ECs. Moreover,
MASP-1 induced bradykinin and histamine receptor expression, and consequently,
increased Ca2+-mobilization was found. Pretreatment with IFNγ enhanced MASP-1-
induced Ca2+-mobilization. Mechanical wounding induced a Ca2+-wave, CREB
phosphorylation and the expression of adhesion molecules on ECs. We found that MASP-
1 can modify the ECs immediate response to wounding (second Ca2+-answer, stronger
CREB phosphorylation, gene expression changes), their participation in the inflammatory
phase (increased VCAM-1 expression) and the later occurring proliferation phase
(disruption of angiogenesis).
Our findings highlight that well-known proinflammatory mediators and MASP-1 can
strongly synergize to enhance the inflammatory response of ECs. Particularly, we found
considerable types of cooperation between MASP-1 and LPS, highlighting the risks of
bacterial infections under conditions where the complement system was already activated
or easily triggered. MASP-1 can also modify the ECs participation in wound healing
processes. Our data suggest that MASP-1 promoting a proinflammatory phenotype can
be beneficial in the early stages, but harmful later as persisting inflammation can lead to
the development of chronic wounds.
