title: Detection of MCP-4 in dermal fibroblasts and its activation of the respiratory burst in human eosinophils.
abstract: CC-chemokines are an important family of proinflammatory mediators that promote the recruitment and activation of human eosinophils in chronic inflammatory diseases. Recently, a novel human CC-chemokine, monocyte chemotactic protein 4 (MCP-4), has been reported that shows amino acid sequence similarities with eotaxin and RANTES, induces chemotaxis of eosinophils, and signals through specific chemokine receptors. In this study, we investigated the effect of MCP-4 on different eosinophil effector functions leading to the activation of the respiratory burst. In human eosinophils, MCP-4 dose dependently induced the production of reactive oxygen species and actin polymerization as a related event. Pretreatment of eosinophils with different enzyme inhibitors interacting with the signal transduction cascade revealed that Gi protein, protein kinase C, tyrosine kinase, and phosphatidylinositol-3-kinase are involved in the signaling following stimulation with MCP-4. In addition, cytokine-stimulated human dermal fibroblasts expressed high levels of MCP-4 mRNA, suggesting that fibroblasts are a physiologic source of MCP-4. Therefore, this study demonstrates that there is an important role of MCP-4 in the activation of eosinophils and that the interaction between dermal fibroblasts and human eosinophils may play an important role within the cytokine network.
authors.affiliation: Department of Dermatology, Hannover Medical School, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Petering
authors.forename: R
authors.initials: R
authors.lastname: Höchstetter
authors.forename: D
authors.initials: D
authors.lastname: Kimmig
authors.forename: R
authors.initials: R
authors.lastname: Smolarski
authors.forename: A
authors.initials: A
authors.lastname: Kapp
authors.forename: J
authors.initials: J
authors.lastname: Elsner
mesh_terms: D000199:Actins / Q000097:blood / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004804:Eosinophils / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D018945:Monocyte Chemoattractant Proteins / Q000032:analysis* / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D016897:Respiratory Burst / Q000187:drug effects / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D012867:Skin / Q000166:cytology / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000199:Actins; C099677:CCL13 protein, human; D004791:Enzyme Inhibitors; D018945:Monocyte Chemoattractant Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma