Reduced iC3b-mediated phagocytotic capacity of pulmonary neutrophils in cystic fibrosis.
Cystic fibrosis (CF) is characterized by a neutrophil-dominated chronic inflammation of the airways with persistent infections. In order to investigate whether neutrophils contribute to an inadequacy in the pulmonary defence mechanism, the phagocytic activity of pulmonary and peripheral blood neutrophils from CF and non-CF respiratory patients were compared. Neutrophils were isolated from both the blood and bronchoalveolar lavage fluid of 21 patients with CF (12 male, 9 female; mean age 7.5 years, range 0.25-16.4 years) and 17 non-CF subjects (9 male, 8 female; mean age 5.4 years, range 0.2-13.1 years). The ex vivo phagocytic rate of normal pulmonary neutrophils to internalize zymosan particles opsonized with iC3b was faster than that of circulating neutrophils (P < 0.05), but the maximum capacity (9 particles/cell) was similar. In contrast, pulmonary neutrophils from patients with CF had a lower phagocytic capacity than circulating neutrophils either from the same patients or from normal subjects. This deficiency could not be attributed to (i) the cell surface density of CR3 (CD18/CD11b) receptors, which were not significantly different between the other groups (ii) the signalling ability of the CR3 receptors, using cytosolic free Ca(2+) signalling as the receptor activity read-out or (iii) a decrease in cellular ATP concentration. As CFTR was not detectable on neutrophils from any source by either histochemistry or Western blotting, it was concluded that the reduced phagocytic capacity was not the direct result of a CFTR mutation, but was attributed to a failure of neutrophil phagocytic priming during translocation into the CF lung.
Morris
M R
MR
Neutrophil Signalling Group, Wales College of Medicine, Cardiff University, UK.
Doull
I J M
IJ
Dewitt
S
S
Hallett
M B
MB
D000255:Adenosine Triphosphate / Q000378:metabolism; D000293:Adolescent; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D018821:CD18 Antigens / Q000276:immunology; D002118:Calcium / Q000276:immunology; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003179:Complement C3b / Q000276:immunology*; D003550:Cystic Fibrosis / Q000276:immunology*; D003600:Cytosol / Q000276:immunology; D005260:Female; D006801:Humans; D007223:Infant; D008168:Lung / Q000276:immunology*; D016177:Macrophage-1 Antigen / Q000276:immunology; D008297:Male; D009504:Neutrophils / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D015054:Zymosan / Q000276:immunology
D018821:CD18 Antigens; D016177:Macrophage-1 Antigen; D003179:Complement C3b; D000255:Adenosine Triphosphate; D015054:Zymosan; D002118:Calcium