title: Elevated levels of the neutrophil chemoattractant pro-platelet basic protein in macrophages from individuals with chronic and allergic aspergillosis.
abstract: BACKGROUND
  Aspergillus fumigatus causes chronic cavitary pulmonary aspergillosis (CCPA) and allergic bronchopulmonary aspergillosis (ABPA) in overtly immunocompetent and atopic individuals, respectively. Disease mechanisms are poorly understood but may be related to increased neutrophil presence and activation. Pro-platelet basic protein (PPBP) is a potent neutrophil chemoattractant and activator whose expression is repressed by interleukin 10 (IL-10).
  
  
  METHODS
  PPBP expression by monocyte-derived macrophages from patients with ABPA or CCPA and asthmatic and healthy controls (10 individuals per group) was analyzed using reverse-transcription polymerase chain reaction. PPBP and IL-10 protein levels in cell culture supernatants were measured by enzyme-linked immunosorbent assay. Two PPBP single-nucleotide polymorphisms (SNPs) were genotyped in 638 individuals. The gene was resequenced in 20 individuals.
  
  
  RESULTS
  PPBP expression and protein levels were significantly increased in the ABPA (19.7-fold) and CCPA (27.7-fold) groups, compared with the control groups. PPBP SNPs were not associated with disease. IL-10 protein levels were significantly lower in the ABPA and CCPA groups, compared with the healthy group, suggesting that differences in PPBP levels may result from regulatory mechanisms.
  
  
  CONCLUSIONS
  The results suggest a role for increased PPBP expression in ABPA and CCPA. Repression of PPBP expression may benefit some patients. Increased PPBP expression in ABPA and CCPA may be useful as a future diagnostic tool or possible target for novel therapeutics.
authors.affiliation: Manchester Fungal Infection Group Manchester Academic Health Science Centre National Aspergillosis Centre, University Hospital South Manchester NHS Foundation Trust NIHR South Manchester Respiratory and Allergy Clinical Research Facility, United Kingdom.
authors.forename: Nicola L D
authors.initials: NL
authors.lastname: Smith
authors.affiliation: Manchester Fungal Infection Group Manchester Academic Health Science Centre National Aspergillosis Centre, University Hospital South Manchester NHS Foundation Trust NIHR South Manchester Respiratory and Allergy Clinical Research Facility, United Kingdom.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bromley
authors.affiliation: Manchester Fungal Infection Group Respiratory and Allergy Centre, Faculty of Medical and Human Science, University of Manchester Manchester Academic Health Science Centre National Aspergillosis Centre, University Hospital South Manchester NHS Foundation Trust NIHR South Manchester Respiratory and Allergy Clinical Research Facility, United Kingdom.
authors.forename: David W
authors.initials: DW
authors.lastname: Denning
authors.affiliation: Respiratory and Allergy Centre, Faculty of Medical and Human Science, University of Manchester Manchester Academic Health Science Centre National Aspergillosis Centre, University Hospital South Manchester NHS Foundation Trust NIHR South Manchester Respiratory and Allergy Clinical Research Facility, United Kingdom.
authors.forename: Angela
authors.initials: A
authors.lastname: Simpson
authors.affiliation: Manchester Fungal Infection Group Manchester Academic Health Science Centre National Aspergillosis Centre, University Hospital South Manchester NHS Foundation Trust NIHR South Manchester Respiratory and Allergy Clinical Research Facility, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Bowyer
mesh_terms: D001228:Aspergillosis / Q000453:epidemiology / Q000276:immunology* / Q000378:metabolism*; D001229:Aspergillosis, Allergic Bronchopulmonary / Q000453:epidemiology / Q000276:immunology* / Q000378:metabolism*; D001232:Aspergillus fumigatus / Q000276:immunology; D016022:Case-Control Studies; D002478:Cells, Cultured; D002908:Chronic Disease; D006801:Humans; D016753:Interleukin-10 / Q000032:analysis / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D001620:beta-Thromboglobulin / Q000032:analysis* / Q000235:genetics / Q000378:metabolism
chemical_list: C061615:PPBP protein, human; D001620:beta-Thromboglobulin; D016753:Interleukin-10
keywords: ABPA; Aspergillus fumigatus; CCPA; PPBP expression; aspergillosis