Neutrophil Functional Heterogeneity: Identification of Competitive Phagocytosis

Hellebrekers, Pien; Hietbrink, Falco; Vrisekoop, Nienke; Leenen, Luke P. H.; Koenderman, Leo

doi:10.3389/fimmu.2017.01498

Cited by 42 publications

(49 citation statements)

References 33 publications

(29 reference statements)

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“…This seems true when the cells are phenotyped by flow cytometry for the expression of markers on their surface. However, when the cells are studied with respect to their phagocytic function, an important complexity emerges . It turns out that cells that are obtained from normal control individuals are very heterogeneous in their capacity to phagocytose bacteria.…”

Section: Heterogeneity Of Cells In Homeostasis: the Concept Of Competmentioning

confidence: 99%

“…However, when the cells are studied with respect to their phagocytic function, an important complexity emerges. 5 It turns out that cells that are obtained from normal control individuals are very heterogeneous in their capacity to phagocytose bacteria. Hellebrekers et al came to the conclusion that all neutrophils can phagocytose bacteria, but some are much better than others.…”

Section: Homeostasis: the Concept Of Competitive Phagocytosismentioning

confidence: 99%

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Neutrophil phenotypes in health and disease

Hellebrekers

Vrisekoop

Koenderman

2018

Eur J Clin Investigation

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Neutrophils are one of the most important effector cells of the innate immune response (1). They are traditionally seen as a homogenous population of short‐lived cells mainly involved in the defence against extracellular microorganisms by phagocytosis and intracellular killing (1,2). The cells contain a large armamentarium that aids in this function and ranges from the production of reactive oxygen species by a membrane‐bound NADPH oxidase to cytotoxic proteins and peptides residing in the different granules present in the cytoplasm (3). Recently, the view of neutrophils belonging to a homogenous population of cells has been challenged, and several neutrophil phenotypes have been described that exhibit specialized functions, such as involvement in tissue repair, tumour killing and immune regulation (4). It is not clear whether these cells belong to separate parallel lineages originating from the bone marrow or that neutrophils become instructed in the distant tissues, thus changing their phenotypes. In addition, functional heterogeneity in a phenotypically homogenous population of neutrophils adds to the complexity of neutrophil phenotypes(5). This article will review the current literature describing the heterogeneity within the neutrophil compartment with respect to both phenotype and function in health and disease.

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Section: Heterogeneity Of Cells In Homeostasis: the Concept Of Competmentioning

confidence: 99%

Section: Homeostasis: the Concept Of Competitive Phagocytosismentioning

confidence: 99%

Neutrophil phenotypes in health and disease

Hellebrekers

Vrisekoop

Koenderman

2018

Eur J Clin Investigation

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“…Although several neutrophil phenotypes exist with specialized functions, phenotypically homogenous populations with functional heterogeneity can be found in health and disease ( 10 ). However, it is unclear whether these cells originate from distinct bone marrow lineages or have undergone local differentiation ( 12 , 13 ).…”

Section: Introductionmentioning

confidence: 99%

Update on Neutrophil Function in Severe Inflammation

et al. 2018

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Neutrophils are main players in the effector phase of the host defense against micro-organisms and have a major role in the innate immune response. Neutrophils show phenotypic heterogeneity and functional flexibility, which highlight their importance in regulation of immune function. However, neutrophils can play a dual role and besides their antimicrobial function, deregulation of neutrophils and their hyperactivity can lead to tissue damage in severe inflammation or trauma. Neutrophils also have an important role in the modulation of the immune system in response to severe injury and trauma. In this review we will provide an overview of the current understanding of neutrophil subpopulations and their function during and post-infection and discuss the possible mechanisms of immune modulation by neutrophils in severe inflammation.

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“…Different neutrophil phenotypes have been described in circulating neutrophils during acute systemic inflammation. [45][46][47][48] Here, we report that local TLF neutrophils obtained from the uncoated ETT group showed an activated neutrophil phenotype as determine by higher mean membrane expression of the adhesion molecules CD62L, CD11a, CD11b, CD18, and CD54, whereas lower expression was observed in the coated group. Interestingly, elevated mean neutrophil adhesion molecule expression has been documented in a variety of medical conditions including those of autoimmune origin.…”

Section: Discussionmentioning

confidence: 70%

Endotracheal intubation results in acute tracheal damage induced by mtDNA/TLR9/NF-κB activity

Puyo

Earhart

Staten

et al. 2018

Journal of Leukocyte Biology

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Tracheitis secondary to placement of an endotracheal tube (ETT) is characterized by neutrophil accumulation in the tracheal lumen, which is generally associated with epithelial damage. Mitochondrial DNA (mtDNA), has been implicated in systemic inflammation and organ dysfunction following trauma; however, less is known about the effects of a foreign body on local trauma and tissue damage. We hypothesized that tracheal damage secondary to the ETT will result in local release of mtDNA at sufficient levels to induce TLR9 and NF‐κB activation. In a swine model we compared the differences between uncoated, and chloroquine (CQ) and N‐acetylcysteine (NAC) coated ETTs as measured by tracheal lavage fluids (TLF) over a period of 6 h. The swine model allowed us to recreate human conditions. ETT presence was characterized by neutrophil activation, necrosis, and release of proinflammatory cytokines mediated by TLR9/NF‐κB induction. Amelioration of the tracheal damage was observed in the CQ and NAC coated ETT group as shown in tracheal tissue specimens and TLF. The role of TLR9/NF‐κB dependent activity was confirmed by HEK‐Blue hTLR9 reporter cell line analysis after coincubation with TLF specimens with predetermined concentrations of NAC or CQ alone or TLR9 inhibitory oligodeoxynucleotide (iODN). These findings indicate that therapeutic interventions aimed at preventing mtDNA/TLR9/NF‐κB activity may have benefits in prevention of acute tracheal damage.

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Neutrophil Functional Heterogeneity: Identification of Competitive Phagocytosis

Cited by 42 publications

References 33 publications

Neutrophil phenotypes in health and disease

Neutrophil phenotypes in health and disease

Update on Neutrophil Function in Severe Inflammation

Endotracheal intubation results in acute tracheal damage induced by mtDNA/TLR9/NF-κB activity

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