Treatment with rhDNase in patients with cystic fibrosis alters in-vitro CHIT-1 activity of isolated leucocytes.
Clin Exp Immunol
; 185(3): 382-91, 2016 09.
Article
in En
| MEDLINE
| ID: mdl-27324468
ABSTRACT
Recent data suggest a possible relationship between cystic fibrosis (CF) pharmacotherapy, Aspergillus fumigatus colonization (AC) and/or allergic bronchopulmonary aspergillosis (ABPA). The aim of this study was to determine if anti-fungal defence mechanisms are influenced by CF pharmacotherapy, i.e. if (1) neutrophils form CF and non-CF donors differ in their ability to produce chitotriosidase (CHIT-1); (2) if incubation of isolated neutrophils with azithromycin, salbutamol, prednisolone or rhDNase might influence the CHIT-1 activity; and (3) if NETosis and neutrophil killing efficiency is influenced by rhDNase. Neutrophils were isolated from the blood of CF patients (n = 19; mean age 26·8 years or healthy, non-CF donors (n = 20; 38·7 years) and stimulated with phorbol-12-myristate-13-acetate (PMA), azithromycin, salbutamol, prednisolone or rhDNase. CHIT-1 enzyme activity was measured with a fluorescent substrate. NETosis was induced by PMA and neutrophil killing efficiency was assessed by a hyphae recovery assay. Neutrophil CHIT-1 activity was comparable in the presence or absence of PMA stimulation in both CF and non-CF donors. PMA stimulation and preincubation with rhDNase increased CHIT-1 activity in culture supernatants from non-CF and CF donors. However, this increase was significant in non-CF donors but not in CF patients (P < 0·05). RhDNase reduced the number of NETs in PMA-stimulated neutrophils and decreased the killing efficiency of leucocytes in our in-vitro model. Azithromycin, salbutamol or prednisolone had no effect on CHIT-1 activity. Stimulation of isolated leucocytes with PMA and treatment with rhDNase interfered with anti-fungal defence mechanisms. However, the impact of our findings for treatment in CF patients needs to be proved in a clinical cohort.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cystic Fibrosis
/
Deoxyribonucleases
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Hexosaminidases
/
Neutrophils
Type of study:
Prognostic_studies
Limits:
Adolescent
/
Adult
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Aged
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Female
/
Humans
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Male
/
Middle aged
Language:
En
Journal:
Clin Exp Immunol
Year:
2016
Document type:
Article