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MASP-1 induces a unique cytokine pattern in endothelial cells: a novel link between complement system and neutrophil

Péter K Jani1, Erika Kajdácsi1, Márton Megyeri2

  • 13rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.

Plos One
|February 4, 2014
PubMed

Insights

Mannan-binding lectin-associated serine protease-1 (MASP-1) activates endothelial cells, prompting them to release IL-6 and IL-8. This cytokine release then enhances neutrophil granulocyte chemotaxis, aiding antimicrobial defense.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Microbial infections require rapid immune responses involving the complement cascade and neutrophils.
  • Mannan-binding lectin-associated serine protease-1 (MASP-1) activates endothelial cells, influencing immune signaling pathways.
  • Neutrophil recruitment is dependent on endothelial cell activation.

Purpose of the Study:

  • To investigate if recombinant MASP-1 (rMASP-1) induces cytokine production in human umbilical vein endothelial cells (HUVECs).
  • To determine if rMASP-1-stimulated HUVECs can promote neutrophil chemotaxis.
  • To elucidate the signaling pathways involved in rMASP-1-mediated endothelial cell activation.

Main Methods:

  • Stimulation of HUVECs with rMASP-1.
  • Measurement of cytokine secretion (IL-6, IL-8, IL-1alpha, IL-1ra, TNFalpha, MCP-1) using ELISA.
  • Assessment of neutrophil chemotaxis using HUVEC supernatant.
  • Analysis of signaling pathways, particularly p38-MAPK.

Main Results:

  • rMASP-1 induced dose-dependent secretion of IL-6 and IL-8 from HUVECs.
  • IL-6 and IL-8 production kinetics varied.
  • The p38-MAPK pathway was the primary regulator of rMASP-1-induced cytokine production.
  • Supernatant from rMASP-1-stimulated HUVECs significantly enhanced neutrophil granulocyte chemotaxis.

Conclusions:

  • MASP-1 activates HUVECs to produce IL-6 and IL-8, predominantly via the p38-MAPK pathway.
  • Activated HUVECs, in turn, promote neutrophil chemotaxis, suggesting an indirect role for MASP-1 in neutrophil activation.
  • MASP-1 links the complement lectin pathway to endothelial cell activation and neutrophil recruitment, contributing to innate antimicrobial defense.

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