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

• Published in: PloS one 2014-01, Vol.9 (1), p.e87104-e87104
• Main Authors: Jani, Péter K, Kajdácsi, Erika, Megyeri, Márton, Dobó, József, Doleschall, Zoltán, Futosi, Krisztina, Tímár, Csaba I, Mócsai, Attila, Makó, Veronika, Gál, Péter, Cervenak, László
• Format: Article
• Language: English
• Subjects: Activation; Antiinfectives and antibacterials; Binding sites; Biology; Calcium signalling; Cell activation; Cell adhesion & migration; Cell growth; Cell migration; Cells, Cultured; Chemokines; Chemotaxis; Chemotaxis, Leukocyte; Complement; Complement Activation; Cyclic AMP Response Element-Binding Protein - metabolism; Cytokines; Cytokines - metabolism; Endothelial cells; Endothelium; Enzymes; Granulocytes; Growth factors; Health aspects; Human Umbilical Vein Endothelial Cells - immunology; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Immune system; Interleukin 1 receptor antagonist; Interleukin 1 receptors; Interleukin 6; Interleukin 8; Internal medicine; Kinases; Kinetics; Lectins; Leukocytes (granulocytic); Leukocytes (neutrophilic); Low density lipoprotein receptors; Mannan; Mannose-binding lectin; Mannose-Binding Protein-Associated Serine Proteases - physiology; MAP kinase; MAP Kinase Kinase 4 - metabolism; MAP Kinase Signaling System; MASP-1 protein; Medical research; Medicine; Microorganisms; Monocyte chemoattractant protein 1; Neutrophil Activation; Neutrophils; Neutrophils - immunology; Neutrophils - metabolism; Pathogens; Phosphorylation; Physiology; Proteins; Serine; Serine proteinase; Thrombin; Umbilical vein
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0087104

Microbial infection urges prompt intervention by the immune system. The complement cascade and neutrophil granulocytes are the predominant contributors to this immediate anti-microbial action. We have previously shown that mannan-binding lectin-associated serine protease-1 (MASP-1), the most abundant enzyme of the complement lectin pathway, can induce p38-MAPK activation, NFkappaB signaling, and Ca(2+)-mobilization in endothelial cells. Since neutrophil chemotaxis and transmigration depends on endothelial cell activation, we aimed to explore whether recombinant MASP-1 (rMASP-1) is able to induce cytokine production and subsequent neutrophil chemotaxis in human umbilical vein endothelial cells (HUVEC). We found that HUVECs activated by rMASP-1 secreted IL-6 and IL-8, but not IL-1alpha, IL-1ra, TNFalpha and MCP-1. rMASP-1 induced dose-dependent IL-6 and IL-8 production with different kinetics. rMASP-1 triggered IL-6 and IL-8 production was regulated predominantly by the p38-MAPK pathway. Moreover, the supernatant of rMASP-1-stimulated HUVECs activated the chemotaxis of neutrophil granulocytes as an integrated effect of cytokine production. Our results implicate that besides initializing the complement lectin pathway, MASP-1 may activate neutrophils indirectly, via the endothelial cells, which link these effective antimicrobial host defense mechanisms.