Mannose-binding lectin without the aid of its associated serine proteases alters lipopolysaccharide-mediated cytokine/chemokine secretion from human endothelial cells.
Coupling between certain pathogen-associated molecular patterns and corresponding pattern recognition receptors of endothelial cells is important for the mediation of vascular inflammatory responses. Mannose-binding lectin (MBL) recognizes certain carbohydrate structures of microbes and subsequently activates the complement system as well as facilitates the phagocytosis of targets. We investigated whether MBL can intervene in the interaction between bacterial lipopolysaccharide (LPS) and endothelial cells to modulate subsequent inflammatory responses. In response to LPS, human umbilical vein endothelial cells (HUVEC) produced various cytokines/chemokines. Addition of the purified human MBL/MBL-associated serine proteases (MASP) complex or recombinant human MBL enhanced LPS-mediated cytokine/chemokine secretion by HUVEC, including interleukin-8 (IL-8), IL-6 and monocyte chemoattractant protein-1 in a dose-dependent manner. This enhancing effect was ameliorated by the addition of anti-MBL antibody or mannan. Among the cytokines/chemokines we analysed, IL-6 showed the greatest increase of secretion in the presence of native MBL/MASP complex or recombinant MBL. MBL, regardless of its association with MASP, alters LPS-mediated cytokine/chemokine secretion of HUVEC. Besides the well-known functions of MBL, to activate the lectin-complement pathway and to facilitate clearance of targets, alteration of cytokine/chemokine secretion may provide an additional role for MBL in modulating vascular inflammation.
Kang
Hee Jung
HJ
Department of Laboratory Medicine, Hallym University College of Medicine, Anyang, Korea. kangheejung@hallym.ac.kr
Lee
Sun-Mi
SM
Lee
Hyeon-Hwa
HH
Kim
Ji Yeon
JY
Lee
Byung-Chul
BC
Yum
Jung-Sun
JS
Moon
Hong Mo
HM
Lee
Bok Luel
BL
D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D042783:Endothelial Cells / Q000276:immunology*; D004730:Endothelium, Vascular / Q000276:immunology*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D037601:Mannose-Binding Lectin / Q000276:immunology*; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D018925:Chemokines; D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D037601:Mannose-Binding Lectin; D011994:Recombinant Proteins; D050606:Mannose-Binding Protein-Associated Serine Proteases