MASP-1 induces a unique cytokine pattern in endothelial cells: a novel link between complement system and neutrophil granulocytes.
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.
3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
Péter K
PK
Jani
3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
Erika
E
Kajdácsi
Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.
Márton
M
Megyeri
Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.
József
J
Dobó
Department of Pathogenetics, National Institute of Oncology, Budapest, Hungary.
Zoltán
Z
Doleschall
Department of Physiology, Semmelweis University School of Medicine, Budapest, Hungary.
Krisztina
K
Futosi
Department of Physiology, Semmelweis University School of Medicine, Budapest, Hungary.
Csaba I
CI
Tímár
Department of Physiology, Semmelweis University School of Medicine, Budapest, Hungary.
Attila
A
Mócsai
3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
Veronika
V
Makó
Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.
Péter
P
Gál
3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
László
L
Cervenak
D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D003167:Complement Activation; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D020935:MAP Kinase Signaling System; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000502:physiology*; D018375:Neutrophil Activation; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism
C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D016207:Cytokines; D048670:MAP Kinase Kinase 4; C084067:MASP1 protein, human; D050606:Mannose-Binding Protein-Associated Serine Proteases