Retinoic acid induces hypersegmentation and enhances cytotoxicity of neutrophils against cancer cells

Shrestha, Sanjeeb; Kim, Shin-Yeong; Yun, Young-Jin; Kim, Jun-Kyu; Lee, Jae Man; Shin, Minsang; Song, Dong‐Keun; Hong, Chang-Won

doi:10.1016/j.imlet.2017.01.001

Cited by 28 publications

(28 citation statements)

References 38 publications

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“…Interestingly, elderly neutrophils exhibited a hypersegmented nuclear morphology, a process dependent on mTOR pathway, which mediates several other neutrophil functions including chemotaxis and cytokine production. Nuclear hypersegmentation is also a distinct characteristic of antitumoral neutrophils characterized by a marked cytotoxic and proinflammatory phenotype . Consistent with this, we observed upregulation of the cytoplasmic granule integrin CD11b, and the ICAM‐1 endothelial adhesion molecule by neutrophils from elderly mice, suggesting increased degranulation .…”

Section: Discussionsupporting

confidence: 86%

Aged neutrophils accumulate in lymphoid tissues from healthy elderly mice and infiltrate T‐ and B‐cell zones

et al. 2018

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The average age of the human population is rising, leading to an increasing burden of age-related diseases, including increased susceptibility to infection. However, immune function can decrease with age which could impact on processes that require a functional immune system. Aging is also characterized by chronic low-grade inflammation which could further impact immune cell function. While changes to neutrophils in blood during aging have been described, little is known in aging lymphoid organs. This study used female C57BL/6J mice comparing bone marrow (BM), spleen and lymph nodes from young mice aged 2-3 months (equivalent to 18 human years) with healthy elderly mice aged 22-24 months (equivalent to 60-70 human years). Neutrophil proportions increased in BM and secondary lymphoid organs of elderly mice relative to their younger counterparts and presented an atypical phenotype. Interestingly, neutrophils from elderly spleen and lymph nodes were long lived (with decreased apoptosis via Annexin V staining and increased proportion of BrdU mature cells) with splenic neutrophils also demonstrating a hypersegmented morphology. Furthermore, splenic neutrophils of elderly mice expressed a mixed phenotype with increased expression of activation markers, CD11b and ICAM-1, increased proinflammatory TNFα, yet increased anti-inflammatory transforming growth factor-beta. Elderly splenic architecture was compromised, as the marginal zone (required for clearing infections) was contracted. Moreover, neutrophils from elderly but not young mice accumulated in lymph node and splenic T- and B-cell zones. Overall, the expansion of functionally compromised neutrophils could contribute to increased susceptibility to infection observed in the elderly.

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Section: Discussionsupporting

confidence: 86%

Aged neutrophils accumulate in lymphoid tissues from healthy elderly mice and infiltrate T‐ and B‐cell zones

et al. 2018

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“…Type I interferons have recently been shown to promote a proinflammatory subset of neutrophils (N1, antitumorigenic) which display an enhanced ability to form NETs [34]. Likewise, Shrestha et al [35] used retinoic acid to drive neutrophil nuclear hypersegmentation, a characteristic finding of N1 cell morphology, and found that retinoic acid treatment also resulted in the augmented release of NETs in response to PMA stimulation. In both studies, the NET-producing, N1 neutrophils also exhibited an increased capacity for cytotoxicity against cancer cells.…”

Section: Noted Thatmentioning

confidence: 99%

“…In both studies, the NET-producing, N1 neutrophils also exhibited an increased capacity for cytotoxicity against cancer cells. Shrestha et al [35] demonstrated that the addition of DNase reversed this effect, suggesting an antitumor role for NETs. Additionally, Villanueva et al [36] demonstrated that a subset of "low-density granulocytes" isolated from patients with SLE had a greater capacity to produce NETs than normal-density neutrophils from patients with SLE or control neutrophils from patients without SLE.…”

Section: Noted Thatmentioning

confidence: 99%

Macrophage Extracellular Traps: A Scoping Review

Doster

Rogers²,

Gaddy³

et al. 2017

J Innate Immun

181

148

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Tissue macrophages are derived from either circulating blood monocytes that originate in the bone marrow, or embryonic precursors that establish residence in tissues and are maintained independent of bone marrow progenitors. Macrophages perform diverse functions including tissue repair, the maintenance of homeostasis, and immune regulation. Recent studies have demonstrated that macrophages produce extracellular traps (ETs). ETs are an immune response by which a cell undergoes “ETosis” to release net-like material, with strands composed of cellular DNA that is studded with histones and cellular proteins. ETs are thought to immobilize and kill microorganisms, but also been implicated in disease pathology including aseptic inflammation and autoimmune disease. We conducted a scoping review to define what is known from the existing literature about the ETs produced by monocytes or macrophages. The results suggest that macrophage ETs (METs) are produced in response to various microorganisms and have similar features to neutrophil ETs (NETs), in that METs are produced by a unique cell death program (METosis), which results in release of fibers composed of DNA and studded with cellular proteins. METs function to immobilize and kill some microorganisms, but may also play a role in disease pathology.

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“…Song, C.W. Hong, 2017) [1]. This article complements the potential of retinoic acid to induce changes in effector function of human neutrophils.…”

mentioning

confidence: 86%

“…The data includes information regarding the effect of retinoic acid on neutrophils complementing the previous study [1]. The apoptosis rates of neutrophils exposed to either retinoic acid (100 nM) or vehicle were examined using annexin/ propidium iodide (PI) fluorescence-activated cell sorting (FACS) staining (Fig.…”

Section: Datamentioning

confidence: 99%

Dataset on the changes of neutrophils treated with retinoic acid

et al. 2017

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The data presented in this article are related to the research article entitled “Retinoic acid induces hypersegmentation and enhances cytotoxicity of neutrophils against cancer cells” (S. Shrestha, S.Y. Kim, Y.J. Young, J.K. Kim, J.M. Lee, M. Shin, D.K. Song, C.W. Hong, 2017) [1]. This article complements the potential of retinoic acid to induce changes in effector function of human neutrophils. Here the datasets describe the rate of apoptosis, changes in numbers of nuclear lobes, and the expressions of surface markers in human neutrophils in presence or absence of retinoic acid. The tumor growth in recipient mice with adoptive transfer of retinoic acid-treated neutrophils was evaluated. The included data is made publicly available to criticism and extended analysis.

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Retinoic acid induces hypersegmentation and enhances cytotoxicity of neutrophils against cancer cells

Cited by 28 publications

References 38 publications

Aged neutrophils accumulate in lymphoid tissues from healthy elderly mice and infiltrate T‐ and B‐cell zones

Aged neutrophils accumulate in lymphoid tissues from healthy elderly mice and infiltrate T‐ and B‐cell zones

Macrophage Extracellular Traps: A Scoping Review

Dataset on the changes of neutrophils treated with retinoic acid

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