title: Osteopontin is increased in cystic fibrosis and can skew the functional balance between ELR-positive and ELR-negative CXC-chemokines.
abstract: BACKGROUND
  The glycoprotein osteopontin plays important roles in several states of disease associated with inflammation, for example by recruiting neutrophils but its expression and possible roles in cystic fibrosis (CF) have not been investigated.
  
  
  METHODS
  Immunohistochemistry and ELISA were used to detect osteopontin in clinical samples. In addition, osteopontin-binding and functional interference with antibacterial (ELR-negative) and neutrophil-recruiting (ELR-positive) CXC-chemokines were investigated using in vitro assays.
  
  
  RESULTS
  Increased osteopontin-expression was found in the airways of CF patients compared with controls. Interestingly, osteopontin bound to ELR-negative CXC-chemokines, reducing their antibacterial and receptor-activating properties while no binding or interference with the function of ELR-positive chemokines was found.
  
  
  CONCLUSIONS
  High expression of osteopontin is likely part of the dysregulated inflammation seen in CF, impairing the activities of ELR-negative chemokines that both serve as innate antibiotics and recruit NK and cytotoxic T cells, instead promoting an excessive influx of neutrophils, and may thus contribute to disease progress.
authors.affiliation: Respiratory Medicine & Allergology, Department of Clinical Sciences Lund, Lund University, Skåne University Hospital, SE-221 85 Lund, Sweden. Electronic address: Sandra.Jovic@med.lu.se.
authors.forename: Sandra
authors.initials: S
authors.lastname: Jovic
authors.affiliation: Respiratory Medicine & Allergology, Department of Clinical Sciences Lund, Lund University, Skåne University Hospital, SE-221 85 Lund, Sweden.
authors.forename: Medya
authors.initials: M
authors.lastname: Shikhagaie
authors.affiliation: Infection Medicine, Department of Clinical Sciences Lund, Lund University, Skåne University Hospital, SE-221 85 Lund, Sweden.
authors.forename: Matthias
authors.initials: M
authors.lastname: Mörgelin
authors.affiliation: Respiratory Medicine & Allergology, Department of Clinical Sciences Lund, Lund University, Skåne University Hospital, SE-221 85 Lund, Sweden.
authors.forename: Jonas S
authors.initials: JS
authors.lastname: Erjefält
authors.affiliation: Department of Biochemistry and Structural Biology, Center for Molecular and Protein Science, Institute for Chemistry and Chemical Engineering, Lund University, SE-221 00 Lund, Sweden.
authors.forename: Sven
authors.initials: S
authors.lastname: Kjellström
authors.affiliation: Respiratory Medicine & Allergology, Department of Clinical Sciences Lund, Lund University, Skåne University Hospital, SE-221 85 Lund, Sweden.
authors.forename: Arne
authors.initials: A
authors.lastname: Egesten
mesh_terms: D016022:Case-Control Studies; D019743:Chemokines, CXC / Q000502:physiology*; D003550:Cystic Fibrosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008168:Lung / Q000378:metabolism*; D020556:Neutrophil Infiltration / Q000502:physiology; D053495:Osteopontin / Q000378:metabolism*; D013183:Sputum / Q000378:metabolism
chemical_list: D019743:Chemokines, CXC; D053495:Osteopontin
keywords: Chemokines; Cystic fibrosis; Host defense; Neutrophils; Osteopontin