title: Complement MASP-1 enhances adhesion between endothelial cells and neutrophils by up-regulating E-selectin expression.
abstract: The complement system and neutrophil granulocytes are indispensable in the immune response against extracellular pathogens such as bacteria and fungi. Endothelial cells also participate in antimicrobial immunity largely by regulating the homing of leukocytes through their cytokine production and their pattern of cell surface adhesion molecules. We have previously shown that mannan-binding lectin-associated serine protease-1 (MASP-1), a complement lectin pathway enzyme, is able to activate endothelial cells by cleaving protease activated receptors, which leads to cytokine production and enables neutrophil chemotaxis. Therefore, we aimed to investigate how recombinant MASP-1 (rMASP-1) can modify the pattern of P-selectin, E-selectin, ICAM-1, ICAM-2, and VCAM-1 adhesion molecules in human umbilical vein endothelial cells (HUVEC), and whether these changes can enhance the adherence between endothelial cells and neutrophil granulocyte model cells (differentiated PLB-985). We found that HUVECs activated by rMASP-1 decreased the expression of ICAM-2 and increased that of E-selectin, whereas ICAM-1, VCAM-1 and P-selectin expression remained unchanged. Furthermore, these changes resulted in increased adherence between differentiated PLB-985 cells and endothelial cells. Our finding suggests that complement MASP-1 can increase adhesion between neutrophils and endothelial cells in a direct fashion. This is in agreement with our previous finding that MASP-1 increases the production of pro-inflammatory cytokines (such as IL-6 and IL-8) and chemotaxis, and may thereby boost neutrophil functions. This newly described cooperation between complement lectin pathway and neutrophils via endothelial cells may be an effective tool to enhance the antimicrobial immune response.
authors.affiliation: 3rd Department of Internal Medicine, Semmelweis University, 1125 Budapest, Hungary.
authors.forename: Péter K
authors.initials: PK
authors.lastname: Jani
authors.affiliation: 3rd Department of Internal Medicine, Semmelweis University, 1125 Budapest, Hungary.
authors.forename: Endre
authors.initials: E
authors.lastname: Schwaner
authors.affiliation: 3rd Department of Internal Medicine, Semmelweis University, 1125 Budapest, Hungary.
authors.forename: Erika
authors.initials: E
authors.lastname: Kajdácsi
authors.affiliation: 3rd Department of Internal Medicine, Semmelweis University, 1125 Budapest, Hungary.
authors.forename: Márta L
authors.initials: ML
authors.lastname: Debreczeni
authors.affiliation: Doctoral School of Molecular and Nanotechnologies, University of Pannonia, 8200 Veszprém, Hungary; Nanobiosensorics Lendület Group, Institute for Technical Physics and Materials Science, Centre for Energy Research, 1121 Budapest, Hungary; Department of Biological Physics, Eötvös Loránd University, 1053 Budapest, Hungary.
authors.forename: Rita
authors.initials: R
authors.lastname: Ungai-Salánki
authors.affiliation: Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, 1117 Budapest, Hungary.
authors.forename: József
authors.initials: J
authors.lastname: Dobó
authors.affiliation: Department of Pathogenetics, National Institute of Oncology, 1122 Budapest, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Doleschall
authors.affiliation: First Department of Obstetrics and Gynecology, Semmelweis University, 1088 Budapest, Hungary.
authors.forename: János
authors.initials: J
authors.lastname: Rigó
authors.affiliation: Department of Physiology, Semmelweis University, 1094 Budapest, Hungary.
authors.forename: Miklós
authors.initials: M
authors.lastname: Geiszt
authors.affiliation: Nanobiosensorics Lendület Group, Institute for Technical Physics and Materials Science, Centre for Energy Research, 1121 Budapest, Hungary; Department of Biological Physics, Eötvös Loránd University, 1053 Budapest, Hungary.
authors.forename: Bálint
authors.initials: B
authors.lastname: Szabó
authors.affiliation: Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, 1117 Budapest, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Gál
authors.affiliation: 3rd Department of Internal Medicine, Semmelweis University, 1125 Budapest, Hungary. Electronic address: cervenak.laszlo@med.semmelweis-univ.hu.
authors.forename: László
authors.initials: L
authors.lastname: Cervenak
mesh_terms: D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D019040:E-Selectin / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D009504:Neutrophils / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D015815:Cell Adhesion Molecules; D019040:E-Selectin; D011994:Recombinant Proteins; C546936:SELE protein, human; C084067:MASP1 protein, human; D050606:Mannose-Binding Protein-Associated Serine Proteases
keywords: Adhesion; Complement; Endothelial cell; Inflammation; MASP-1; Neutrophil