Elevated levels of the neutrophil chemoattractant PPBP in macrophages from individuals with chronic and allergic aspergillosis

Nicola L. D. Smith, Michael J. Bromley, D W Denning, Angela Simpson, Paul Bowyer

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)651–660
Number of pages10
JournalThe Journal of Infectious Diseases
Volume211
Issue number4
Early online date5 Sept 2014
DOIs
Publication statusPublished - 15 Feb 2015

Keywords

  • PPBP expression
  • aspergillosis
  • ABPA
  • CCPA
  • aspergillus fumigatus

Fingerprint

Dive into the research topics of 'Elevated levels of the neutrophil chemoattractant PPBP in macrophages from individuals with chronic and allergic aspergillosis'. Together they form a unique fingerprint.

Cite this