Reprogramming of a subpopulation of human blood neutrophils by prolonged exposure to cytokines

被引：41

作者：

Chakravarti, Arpita ^{[1
]}

Rusu, Daniel ^{[1
]}

Flamand, Nicolas ^{[2
]}

Borgeat, Pierre ^{[1
]}

Poubelle, Patrice E. ^{[1
]}

机构：

[1] Univ Laval, CRCHUL, Fac Med, CRRI,Dept Med, Quebec City, PQ G1V 4G2, Canada

[2] Hop Laval, Dept Med, Ctr Rech, Quebec City, PQ, Canada

来源：

LABORATORY INVESTIGATION | 2009年 / 89卷 / 10期

基金：

加拿大健康研究院;

关键词：

inflammation; innate; acquired immunity; survival; COLONY-STIMULATING FACTOR; ACTIVATED HUMAN NEUTROPHILS; SYNOVIAL-FLUID NEUTROPHILS; GLYCOGEN-SYNTHASE KINASE-3; EARLY RHEUMATOID-ARTHRITIS; PROGRAMMED CELL-DEATH; POLYMORPHONUCLEAR NEUTROPHILS; T-CELLS; IMMUNE-RESPONSES; LEUKOTRIENE B-4;

D O I：

10.1038/labinvest.2009.74

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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-a 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-1 beta. 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. Laboratory Investigation (2009) 89, 1084-1099; doi:10.1038/labinvest.2009.74; published online

引用

页码：1084 / 1099

页数：16