Reprogramming of a subpopulation of human blood neutrophils by prolonged exposure to cytokines.
Lab Invest
; 89(10): 1084-99, 2009 Oct.
Article
en En
| MEDLINE
| ID: mdl-19636293
ABSTRACT
Essential cells of innate immunity, neutrophils are often considered to be a homogenous population of terminally differentiated cells. During inflammation, neutrophils are extravasated cells exposed to local factors that prolong their survival and activate their production of mediators implicated in disease progression. In this study, a phenotypically distinct subset of human neutrophils that appear after prolonged exposure to cytokines was characterized. Freshly isolated neutrophils from healthy donors were incubated with granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha and interleukin (IL)-4, three cytokines that are locally present in various inflammatory conditions. Eight to 17% of neutrophils survived beyond 72 h. This subset of non-apoptotic neutrophils, as evaluated by three different markers, was enriched by discontinuous Percoll gradient centrifugation before studying their phenotype. These viable neutrophils showed neoexpression of HLA-DR, CD80 and CD49d. Compared with freshly isolated neutrophils, they responded differentially to second signals similar to formyl-methionyl-leucyl-phenylalanine with three- to four-fold increases in production of superoxide anions and leukotrienes. These cells augmented their phagocytic index by 141%, increased their adhesion to human primary fibroblasts, but reduced their migration in response to chemotactic stimuli and decreased exocytosis of primary and secondary granules. In addition, they produced substantial amounts of IL-8, IL-1Ra and IL-1beta. This neutrophil subset had a unique profile of phosphorylation of intracellular signaling molecules. In conclusion, the present identification of a novel neutrophil phenotype highlights the reprogammable character of the neutrophil. This aspect is crucial for our understanding of its contribution to disease pathogenesis and host defense.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Factor Estimulante de Colonias de Granulocitos y Macrófagos
/
Interleucina-4
/
Factor de Necrosis Tumoral alfa
/
Inflamación
/
Neutrófilos
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Lab Invest
Año:
2009
Tipo del documento:
Article
País de afiliación:
Canadá