title: Mouse mannose-binding lectin-A and ficolin-A inhibit lipopolysaccharide-mediated pro-inflammatory responses on mast cells.
abstract: It is unknown how soluble pattern-recognition receptors in blood, such as mannose-binding lectin (MBL) and ficolins, modulate mast cell-mediated inflammatory responses. We investigate how mouse MBL-A or ficolin-A regulate mouse bone marrow-derived mast cells (mBMMCs)-derived inflammatory response against bacterial lipopolysaccharide (LPS) stimulation. LPS-mediated pro-inflammatory cytokine productions on mBMMCs obtained from Toll-like receptor4 (TLR4)-deficient mice, TLR2-defficient mice, and their wildtype, were specifically attenuated by the addition of either mouse MBL-A or ficolin-A in a dose-dependent manner. However, the inhibitory effects by mouse MBL-A or ficolin-A were restored by the addition of mannose or N-acetylglucosamine, respectively. These results suggest that mouse MBL-A and ficolin-A bind to LPS via its carbohydrate-recognition domain and fibrinogen-like domain, respectively, whereby cytokine production by LPS-mediated TLR4 in mBMMCs appears to be down-regulated, indicating that mouse MBL and ficolin may have an inhibitory function toward mouse TLR4-mediated excessive inflammation on the mast cells.
authors.affiliation: The Global Research Laboratory of Insect Symbiosis, College of Pharmacy, Pusan National University, Busan 609-735, Korea.
authors.forename: Ying Jie
authors.initials: YJ
authors.lastname: Ma
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Kang
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Kim
authors.forename: Peter
authors.initials: P
authors.lastname: Garred
authors.forename: Myung-Shik
authors.initials: MS
authors.lastname: Lee
authors.forename: Bok Luel
authors.initials: BL
authors.lastname: Lee
mesh_terms: D000117:Acetylglucosamine / Q000494:pharmacology; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D037102:Lectins / Q000378:metabolism / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000378:metabolism / Q000633:toxicity; D008358:Mannose / Q000494:pharmacology; D037601:Mannose-Binding Lectin / Q000378:metabolism / Q000494:pharmacology*; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011485:Protein Binding; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D000097604:Ficolins
chemical_list: D000117:Acetylglucosamine; D016207:Cytokines; D018836:Inflammation Mediators; D015850:Interleukin-6; D037102:Lectins; D008070:Lipopolysaccharides; D008358:Mannose; D037601:Mannose-Binding Lectin; D051197:Toll-Like Receptor 4; D000097604:Ficolins