Neutrophil-like low-density granulocytes are elevated in patients with moderate to severe persistent asthma

Fu, Jun; Tobin, Mary C.; Thomas, Larry L.

doi:10.1016/j.anai.2014.08.024

Cited by 58 publications

(56 citation statements)

References 22 publications

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“…In asthmatic patients, LDNs have been reported to contain a mixture of activated mature neutrophils (e.g. displaying higher levels of CD11b and CD66b than autologous NDNs) and immature neutrophils (mostly band cells), but no functional data were shown in that study . LDNs from P. vivax ‐infected patients have been shown instead to display a more activated phenotype than autologous NDNs (as revealed by their enhanced CD66b and CD15 expression), but a similar type I interferon transcriptional signature, an altered migration toward CCL3 and CXCL8 and an increased phagocytic activity .…”

Section: Low Density Neutrophilsmentioning

confidence: 87%

Human neutrophils in the saga of cellular heterogeneity: insights and open questions

Scapini

Marini

Tecchio

et al. 2016

Immunological Reviews

226

304

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Summary Recent findings have uncovered novel fascinating aspects of the biology of neutrophils, which ultimately attribute to these cells a broader role in inflammation and immunity. One aspect that is currently under intensive investigation is the notion of neutrophil ‘heterogeneity’. Studies examining neutrophils in a variety of acute and chronic inflammatory conditions report, in fact, the recovery of CD66b+ cells displaying neutrophil‐like morphology at different degrees of maturation/activation, able to exert either immunosuppressive or proinflammatory properties. These heterogeneous populations of mature and immature neutrophils are indicated with a variety of names, including ‘low density neutrophils (LDNs)’, ‘low density granulocytes (LDGs)’, ‘granulocytic‐myeloid derived suppressor cells (G‐MDSCs)’, and immunosuppressive neutrophils. However, due to the lack of discrete markers that can unequivocally allow their specific identification and isolation, the precise phenotype and function of all these presumably novel, neutrophil‐like, populations have not been correctly defined yet. Aim of this article is to summarize current knowledge on the mature and immature neutrophil populations described to date, featuring immunosuppressive or proinflammatory properties, often defined as ‘subsets’, as well as to critically discuss unresolved issues in the field.

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Section: Low Density Neutrophilsmentioning

confidence: 87%

Human neutrophils in the saga of cellular heterogeneity: insights and open questions

Scapini

Marini

Tecchio

et al. 2016

Immunological Reviews

226

304

View full text Add to dashboard Cite

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“…The appearance of neutrophils in the PBMC fraction after Ficoll‐Paque centrifugation is described in several inflammatory diseases. However, when different patient groups and different studies are compared, these cells are quite variable in both phenotype and functionality 3,9,20,24,25 . In the following paragraphs, the different subsets of LDNs are described, supplemented with our own data.…”

Section: Ldns In Disease Are Heterogeneousmentioning

confidence: 99%

On the origin of low-density neutrophils

Hassani

Hellebrekers

Chen

et al. 2020

Journal of Leukocyte Biology

100

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Here we elaborate on the origin of low(er)-density neutrophils (LDNs) to better understand the variation found in literature. Supplemented with original data, we test the hypothesis that buoyant density of neutrophils is characterized by a spectrum that as a whole shifts to a lower density after activation. Both the 20% highest density (HDNs) and 20% lowest density (LDNs) neutrophils from healthy donors were isolated by Percoll of different densities. Using this method we found that LDNs were significantly better in T-cell suppression and bacterial containment than their 20% highest density counterparts. We found no statistically relevant differences in neutrophil survival or bacterial phagocytosis. Stimulation of healthy donor neutrophils with N-formylmethionyl-leucyl-phenylalanine induced LDNs co-segregating with peripheral blood mononuclear cells after Ficoll separation. These in vitro induced LDNs showed increased activation markers compared to HDNs and were comparable to the activation markers found on the LDN fraction seen in patients with chronic inflammatory conditions such as present in cancer patients. This all fits with the hypothesis that the density of neutrophils is distributed in a spectrum partially coupled to maturation. Additionally a shift in this spectrum can be induced by in vitro stimulation or by activation in disease. K E Y W O R D Sgranulocytes, LDG, neutrophil subsets INTRODUCTIONNeutrophils are main actors in the innate immune system. Until recently neutrophils were thought to belong to a relative homogeneous population of cells. However, an increasing number of studies now show heterogeneity in morphology, phenotype, function, or a combination of these factors. 1 One of the subtypes of neutrophils identified and studied is the low-density neutrophil (LDN). It was first recognized in 1986, when neutrophils co-segregated with mononuclear cells after density-gradient isolation in systemic lupus erythematosus (SLE) and rheumatoid arthritis patients. 2 Thereafter, the presence of LDNs have been shown in several, mostly chronic, diseases. 3

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“…However, during acute and chronic inflammation a population of neutrophils with altered buoyancy characteristics colocalizes with the PBMC lower density fraction and as such has been collectively termed low‐density neutrophils (LDNs). Although first described in autoimmunity examples of elevated LDN numbers have spread to a variety of settings including cancer, infection, asthma, sepsis, graft versus host disease, and pregnancy . The overall function of these cells appears to be dependent on inflammatory stimuli and LDN numbers often correlate with disease progression in human patients .…”

Section: Neutrophil Populations In Inflammatory Settingsmentioning

confidence: 99%

Neutrophil heterogeneity: Bona fide subsets or polarization states?

Deniset

Kubes

2018

Journal of Leukocyte Biology

122

125

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Neutrophils are key components of the innate immune system that play important roles during infection, injury, and chronic disease. In recent years, neutrophil heterogeneity has become an emerging focus with accumulating evidence of neutrophil populations with distinct functions under both steady-state and pathologic conditions. Despite these advances, it remains unclear whether these different populations represent bona fide subsets or simply activation/polarization states in response to local cues. In this review, we summarize the varied neutrophils populations that have been described under both basal and during inflammation. We discuss the evidence that supports the existence of neutrophils subsets. Finally, we identify potential gaps in our knowledge that may further advance our current understanding of neutrophil heterogeneity.

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Neutrophil-like low-density granulocytes are elevated in patients with moderate to severe persistent asthma

Cited by 58 publications

References 22 publications

Human neutrophils in the saga of cellular heterogeneity: insights and open questions

Human neutrophils in the saga of cellular heterogeneity: insights and open questions

On the origin of low-density neutrophils

Neutrophil heterogeneity: Bona fide subsets or polarization states?

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