title: The detection of ADAM8 protein on cells of the human immune system and the demonstration of its expression on peripheral blood B cells, dendritic cells and monocyte subsets.
abstract: A disintegrin and metalloprotease (ADAM) proteins have wide ranging functions, including proteolytic cleavage of cell surface molecules, cell fusion, cell adhesion and intracellular signalling. Recent evidence suggests the involvement of ADAM8 in allergic responses. For instance, ADAM8 is amongst a number of genes up-regulated in experimentally induced asthma in animals. In order to further define the involvement of ADAM8 in allergic responses, we sought in the first instance to examine its distribution on human peripheral blood B cells, resting and activated T cells, monocyte subsets and monocyte derived dendritic cells. Here we demonstrate for the first time ADAM8 protein expression on B cells and dendritic cells, and its higher expression on CD14(2+)CD16(-) monocytes compared to CD14(+)CD16(+) cells. Immature dendritic cells expressed low levels of ADAM8 when treated with a combination of GM-CSF and IL-4, but stimulation with LPS resulted in a higher level of expression, which was TLR-4 independent. Up-regulation of ADAM8 expression on dendritic cells was also observed after stimulation with TNF-alpha, but not after stimulation with anti-CD40. The demonstration of ADAM8 expression on these cells provides an opportunity for addressing the potential role of inhaled protease allergens, such as Der p 1, in modulating ADAM8 functions, particularly with regards to innate immune responses by dendritic cells and IgE synthesis by B cells.
authors.affiliation: Institute of Infection, Immunity and Inflammation, School of Molecular Medical Sciences, University of Nottingham, Nottingham, UK.
authors.forename: Joanna
authors.initials: J
authors.lastname: Richens
authors.forename: Lucy
authors.initials: L
authors.lastname: Fairclough
authors.forename: Amir M
authors.initials: AM
authors.lastname: Ghaemmaghami
authors.forename: Jafar
authors.initials: J
authors.lastname: Mahdavi
authors.forename: Farouk
authors.initials: F
authors.lastname: Shakib
authors.forename: Herbert F
authors.initials: HF
authors.lastname: Sewell
mesh_terms: D051722:ADAM Proteins / Q000276:immunology / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D015153:Blotting, Western; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D018950:Lipopolysaccharide Receptors; D008565:Membrane Proteins; D017452:Receptors, IgG; D051722:ADAM Proteins; C068490:ADAM8 protein, human