title: Osteopontin binds and modulates functions of eosinophil-recruiting chemokines.
abstract: BACKGROUND
  Allergic asthma is characterized by eosinophilic inflammation and airway obstruction. There is also an increased risk of pulmonary infection caused by Streptococcus pneumoniae, in particular during severe asthma where high levels of the glycoprotein, osteopontin (OPN), are present in the airways. Eosinophils can be recruited by chemokines activating the receptor CCR3 including eotaxin-1/CCL11, eotaxin-2/CCL24, eotaxin-3/CCL26, RANTES/CCL5, and MEC/CCL28. In addition to inducing chemotaxis, several of these molecules have defensin-like antibacterial properties. This study set out to elucidate the functional consequences of OPN binding to eosinophil-recruiting chemokines.
  
  
  METHODS
  Antibacterial activities of the chemokines were investigated using viable count assays and electron microscopy. Binding studies were performed by means of surface plasmon resonance. The potential interference of OPN with antibacterial, receptor-activating, and lipopolysaccharide-neutralizing abilities of these chemokines was investigated.
  
  
  RESULTS
  We found that OPN bound all eosinophil-recruiting chemokines with high affinity except for CCL5. The eosinophil-recruiting chemokines all displayed bactericidal activity against S. pneumoniae, but only CCL26 and CCL28 retained high antibacterial activity in the presence of sodium chloride at physiologic concentrations. Preincubation of the chemokines with OPN strongly inhibited their antibacterial activity against S. pneumoniae but did not affect their ability to activate CCR3. All chemokines investigated showed LPS-neutralizing activity that was impaired by OPN only in the case of CCL24.
  
  
  CONCLUSIONS
  The data suggest that OPN may impair host defense activities of the chemokines without affecting their eosinophil-recruiting properties. This could be one mechanism explaining the increased vulnerability to acquire pneumococcal infection in parallel with sustained allergic inflammation in asthma.
authors.affiliation: Division of Respiratory Medicine & Allergology, Department of Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Gela
authors.affiliation: Division of Respiratory Medicine & Allergology, Department of Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Kasetty
authors.affiliation: Division of Infection Medicine, Department of Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Mörgelin
authors.affiliation: Division of Respiratory Medicine & Allergology, Department of Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Bergqvist
authors.affiliation: Division of Respiratory Medicine & Allergology, Department of Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden.
authors.forename: J S
authors.initials: JS
authors.lastname: Erjefält
authors.affiliation: Leukocyte Biology Section, NHLI, Faculty of Medicine, Imperial College of Science, Technology and Medicine, London, UK.
authors.forename: J E
authors.initials: JE
authors.lastname: Pease
authors.affiliation: Division of Respiratory Medicine & Allergology, Department of Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Egesten
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000075906:Chemokine CCL26; D018925:Chemokines / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D019742:Chemokines, CC / Q000737:chemistry / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D004804:Eosinophils / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D053495:Osteopontin / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D054397:Receptors, CCR3 / Q000378:metabolism; D015398:Signal Transduction; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000276:immunology / Q000648:ultrastructure
chemical_list: D000900:Anti-Bacterial Agents; C120429:CCL26 protein, human; D000075906:Chemokine CCL26; D018925:Chemokines; D019742:Chemokines, CC; D008070:Lipopolysaccharides; D054397:Receptors, CCR3; D053495:Osteopontin
keywords: allergy; asthma; chemokines; eosinophils; osteopontin