Nicola L D Smith1, Michael J Bromley1, David W Denning2, Angela Simpson3, Paul Bowyer1. 1. 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. 2. 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. 3. 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.
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.
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: Edwin R Chilvers; Charlotte Summers; Kathleen R Bashant; Angel M Aponte; Davide Randazzo; Paniz Rezvan Sangsari; Alexander Jt Wood; Jack A Bibby; Erin E West; Arlette Vassallo; Zerai G Manna; Martin P Playford; Natasha Jordan; Sarfaraz Hasni; Marjan Gucek; Claudia Kemper; Andrew Conway Morris; Nicole Y Morgan; Nicole Toepfner; Jochen Guck; Nehal N Mehta; Mariana J Kaplan Journal: Ann Rheum Dis Date: 2020-09-28 Impact factor: 19.103
Authors: Lilan Zhao; Anastasios D Giannou; Yang Xu; Ahmad Mustafa Shiri; Imke Liebold; Babett Steglich; Tanja Bedke; Tao Zhang; Jöran Lücke; Pasquale Scognamiglio; Jan Kempski; Anna Woestemeier; Jing Chen; Theodora Agalioti; Dimitra E Zazara; Diana Lindner; Melanie Janning; Jan K Hennigs; Rajesh M Jagirdar; Ourania S Kotsiou; Sotirios G Zarogiannis; Yasushi Kobayashi; Jacob R Izbicki; Sourav Ghosh; Carla V Rothlin; Lidia Bosurgi; Samuel Huber; Nicola Gagliani Journal: Sci Adv Date: 2021-08-13 Impact factor: 14.136