title: Human cord blood-derived mast cells are activated by the Nod1 agonist M-TriDAP to release pro-inflammatory cytokines and chemokines.
abstract: Mast cells are among the first cells of our immune system to encounter exogenous danger. Intracellular receptors such as nucleotide-binding oligomerization domain (Nod) play an important role in responding to invading pathogens. Here, we have investigated the response of human mast cells to the Nod1 ligand M-TriDAP. Human cord blood-derived mast cells (CBMCs) were activated with M-TriDAP alone, or in combination with the Toll-like receptor (TLR) ligands lipopolysaccharide (LPS) and zymosan. Release of pro-inflammatory chemokines and cytokines was measured by ELISA, cytometric bead array and LUMINEX, and degranulation was evaluated by analysis of histamine release. M-TriDAP induced a dose-dependent release of IL-8, MIP-1α, MIP-1β and TNF. In contrast, degranulation could not be observed. When cells were treated with M-TriDAP in combination with the TLR4 agonist LPS, but not with TLR2 agonist zymosan, the secretion of cytokines was augmented. We here present results demonstrating that human CBMCs are stimulated by the Nod1 agonist M-TriDAP alone and in combination with LPS to produce pro-inflammatory cytokines and chemokines. Our results add to the concept that mast cells constitute an important part of our host defense, as they are equipped with several types of important pattern recognition receptors, including TLRs and Nod.
authors.affiliation: Department of Medicine, Clinical Immunology and Allergy Unit, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Mattias
authors.initials: M
authors.lastname: Enoksson
authors.forename: Karin F K
authors.initials: KF
authors.lastname: Ejendal
authors.forename: Sarah
authors.initials: S
authors.lastname: McAlpine
authors.forename: Gunnar
authors.initials: G
authors.lastname: Nilsson
authors.forename: Carolina
authors.initials: C
authors.lastname: Lunderius-Andersson
mesh_terms: D000117:Acetylglucosamine; D018925:Chemokines / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D005312:Fetal Blood / Q000166:cytology* / Q000276:immunology; D006801:Humans; D007249:Inflammation; D008024:Ligands; D008070:Lipopolysaccharides / Q000276:immunology; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism; D009112:Muramic Acids; D053474:Nod1 Signaling Adaptor Protein / Q000819:agonists* / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D010446:Peptide Fragments / Q000276:immunology*; D010457:Peptidoglycan / Q000276:immunology; D013379:Substrate Specificity; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism
chemical_list: D018925:Chemokines; D016207:Cytokines; D008024:Ligands; D008070:Lipopolysaccharides; D009112:Muramic Acids; C119067:NOD1 protein, human; D053474:Nod1 Signaling Adaptor Protein; D010446:Peptide Fragments; D010457:Peptidoglycan; D051193:Toll-Like Receptors; D000117:Acetylglucosamine