title: Myeloid-related proteins-8 and -14 are expressed but dispensable in the pathogenesis of experimental epidermolysis bullosa acquisita and bullous pemphigoid.
abstract: BACKGROUND
  Myeloid-related protein-8 (MRP-8) and its heterodimeric partner, MRP-14 belong to the group of danger-associated molecular patterns (DAMPs) and are associated with numerous chronic human disorders. However, their functional role in autoimmunity remains largely unclear.
  
  
  OBJECTIVE
  Here, we examined the involvement of MRP-8/-14 in two difficult-to-treat autoimmune blistering diseases, epidermolysis bullosa acquisita (EBA) and bullous pemphigoid (BP).
  
  
  METHODS
  MRP-8/-14 concentrations in the sera of EBA and BP patients were quantified by ELISA. Experimental EBA and BP in mice were induced by transfer of antibodies directed against type VII or XVII collagen, respectively. Expression of MRP-8/-14 was analyzed in skin samples of these experimental mouse models. The functional role of MRP-8/-14 proteins was evaluated by the induction of experimental EBA and BP in MRP-14-deficient mice.
  
  
  RESULTS
  We found serum levels of MRP-8/-14 to be elevated in both, EBA and BP patients. Furthermore, in the lesional skin of mice with experimental diseases expression of MRP-8/-14 was increased as compared to healthy controls. However, MRP-14-deficient mice were fully susceptible to experimental disease with a phenotype comparable to that of wild type controls.
  
  
  CONCLUSIONS
  Although MRP-8/-14 expression is highly increased in experimental as well as human disease, these proteins do not contribute to the pathogenesis in the effector phase of EBA and BP.
authors.affiliation: Priority Area Asthma & Allergy, Research Center Borstel, 23845 Borstel, Germany; Airway Research Center North (ARCN), Members of the German Center for Lung Research (DZL), Germany; Lübeck Institute of Experimental Dermatology (LIED), University of Lübeck, Germany.
authors.forename: Reza
authors.initials: R
authors.lastname: Akbarzadeh
authors.affiliation: Priority Area Asthma & Allergy, Research Center Borstel, 23845 Borstel, Germany; Airway Research Center North (ARCN), Members of the German Center for Lung Research (DZL), Germany; Laboratory of Autoimmunity, The Medical College of Xiamen University, Xiamen University, 361005 Xiamen, China.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Yu
authors.affiliation: Institute of Immunology, University of Münster, Münster, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Vogl
authors.affiliation: Lübeck Institute of Experimental Dermatology (LIED), University of Lübeck, Germany.
authors.forename: Ralf J
authors.initials: RJ
authors.lastname: Ludwig
authors.affiliation: Department of Dermatology, University of Lübeck, Lübeck, Germany.
authors.forename: Enno
authors.initials: E
authors.lastname: Schmidt
authors.affiliation: Department of Dermatology, University of Lübeck, Lübeck, Germany.
authors.forename: Detlef
authors.initials: D
authors.lastname: Zillikens
authors.affiliation: Priority Area Asthma & Allergy, Research Center Borstel, 23845 Borstel, Germany; Airway Research Center North (ARCN), Members of the German Center for Lung Research (DZL), Germany. Electronic address: fpetersen@fz-borstel.de.
authors.forename: Frank
authors.initials: F
authors.lastname: Petersen
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000097:blood; D000818:Animals; D040501:Calgranulin A / Q000097:blood / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D040502:Calgranulin B / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D004195:Disease Models, Animal; D016107:Epidermolysis Bullosa Acquisita / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020022:Genetic Predisposition to Disease; D006801:Humans; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010391:Pemphigoid, Bullous / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D015854:Up-Regulation
chemical_list: C435500:ABCC11 protein, human; D018528:ATP-Binding Cassette Transporters; D040501:Calgranulin A; D040502:Calgranulin B; C576329:S100A9 protein, mouse; C086145:S100a8 protein, mouse
keywords: Animal models; Autoimmune bullous disease; Danger-associated molecular pattern; Myeloid-related proteins-8/-14; Neutrophils; Patients