Association of low-density neutrophils with lung function and disease progression in adult cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) neutrophils fail to eradicate infection despite their massive recruitment into the lung. While studies mostly focus on pathogen clearance by normal density neutrophils in CF, the contribution of low-density neutrophil (LDNs) subpopulations to disease pathogenesis remains unclear. METHODS: LDNs were isolated from whole blood donations of clinically stable adult CF patients and from healthy donors. LDN proportion and immunophenotype was assessed by flow cytometry. Associations of LDNs with clinical parameters were determined. RESULTS: LDN proportion was increased in CF patients' circulation compared with healthy donors. LDNs are a heterogeneous population of both mature and immature cells in CF and in healthy individuals. Moreover, a higher proportion of mature LDN correlates with a gradual decline in lung function and repeated pulmonary exacerbations in CF patients. CONCLUSIONS: Collectively, our observations suggest that low-density neutrophils are linked to CF pathogenesis and underscore the potential clinical relevance of neutrophil subpopulations in CF.

Comparison of Neutrophil Function in Granulocyte Concentrates From Prednisone- and G-CSF-Treated Donors: Effect of Stimulant, Leukapheresis and Storage.

Transfusion of granulocyte concentrates (GC) is an alternative therapy for neutropenic patients with life-threatening infections. While neutrophils are the main source of antimicrobial activity, only neutrophil numbers are used to certify GCs. The objective of this study was thus to functionally characterize neutrophils in GCs prepared by leukapheresis from G-CSF-stimulated donors and compare to the less characterized prednisone GCs. GCs prepared from healthy donors stimulated with prednisone and then G-CSF after a 6-month washout period were analyzed prior to and after leukapheresis, and after storage. Leukocyte composition, neutrophil viability, calcium mobilization, chemotaxis, phagocytosis, reactive oxygen species, cytokine production and metabolites were determined. G-CSF GCs contained significantly more neutrophils than prednisone GCs of which 40% were immature. In comparison to non-stimulated healthy donor neutrophils, prednisone GC neutrophils exhibited enhanced phagocytosis and G-CSF GC neutrophils showed decreased chemotaxis but increased IL-8 production. Leukapheresis altered prednisone GC neutrophil responses. Storage had a significant, negative impact on G-CSF GC neutrophils compared to prednisone GC neutrophils. G-CSF and prednisone GC neutrophils thus differ in maturity and function, and G-CSF GC neutrophils are more sensitive to storage. Functional testing of GC neutrophils and better storage conditions would improve the quality of this blood product.