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 Ca(2+) 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.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Molecular Immunology |
| Vol/bind | 59 |
| Nummer | 1 |
| Sider (fra-til) | 39-45 |
| Antal sider | 7 |
| ISSN | 0161-5890 |
| DOI | |
| Status | Udgivet - maj 2014 |
Emneord
- Blotting, Western
- Calcium
- Cells, Cultured
- Complement Activation
- Complement Pathway, Mannose-Binding Lectin
- Human Umbilical Vein Endothelial Cells
- Humans
- Immunity, Innate
- Mannose-Binding Lectin
- Mannose-Binding Protein-Associated Serine Proteases
- Microscopy, Fluorescence
- Mutation
- Peptide Fragments
- Protein Binding
- Proteolysis
- Recombinant Proteins