Multiple Roles for Chemokines in Neutrophil Biology

Capucetti, Arianna; Albano, F.; Bonecchi, Raffaella

doi:10.3389/fimmu.2020.01259

Cited by 165 publications

(129 citation statements)

References 98 publications

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“…In line with results from previous literature, expression levels of certain chemokines were increased after LPS injection in this study; in specific, among the aforementioned chemokines, CXCL1 and CCL2 demonstrated a surge in expression, along with CXCL13, CXCL10, and CCL5. CXCL1 and CCL2 are well-known for their roles in stimulating neutrophil migration, while CXCL10, CCL2, and CCL5 have been reported to be released by neutrophils in inflammatory situations, mostly in order to recruit other innate or adaptive immune cells ( Kobayashi, 2008 ; Sawant et al, 2016 ; Capucetti et al, 2020 ). Therefore, chemokines that are chemotactic for neutrophils, such as CXCL1 or CCL2 may be the principal factor driving the various migratory phenomena observed in this paper: neutrophil extravasation and rTEM.…”

Section: Discussionmentioning

confidence: 99%

Neutrophils Return to Bloodstream Through the Brain Blood Vessel After Crosstalk With Microglia During LPS-Induced Neuroinflammation

Kim

Lee

et al. 2020

Front. Cell Dev. Biol.

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The circulatory neutrophil and brain tissue-resident microglia are two important immune cells involved in neuroinflammation. Since neutrophils that infiltrate through the brain vascular vessel may affect the immune function of microglia in the brain, close investigation of the interaction between these cells is important in understanding neuroinflammatory phenomena and immunological aftermaths that follow. This study aimed to observe how morphology and function of both neutrophils and microglia are converted in the inflamed brain. To directly investigate cellular responses of neutrophils and microglia, LysMGFP/+ and CX3CR1GFP/+ mice were used for the observation of neutrophils and microglia, respectively. In addition, low-dose lipopolysaccharide (LPS) was utilized to induce acute inflammation in the central nervous system (CNS) of mice. Real-time observation on mice brain undergoing neuroinflammation via two-photon intravital microscopy revealed various changes in neutrophils and microglia; namely, neutrophil infiltration and movement within the brain tissue increased, while microglia displayed morphological changes suggesting an activated state. Furthermore, neutrophils seemed to not only actively interact with microglial processes but also exhibit reverse transendothelial migration (rTEM) back to the bloodstream. Thus, it may be postulated that, through crosstalk with neutrophils, macrophages are primed to initiate a neuroinflammatory immune response; also, during pathogenic events in the brain, neutrophils that engage in rTEM may deliver proinflammatory signals to peripheral organs outside the brain. Taken together, these results both show that neuroinflammation results in significant alterations in neutrophils and microglia and lay the pavement for further studies on the molecular mechanisms behind such changes.

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Section: Discussionmentioning

confidence: 99%

Neutrophils Return to Bloodstream Through the Brain Blood Vessel After Crosstalk With Microglia During LPS-Induced Neuroinflammation

Kim

Lee

et al. 2020

Front. Cell Dev. Biol.

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“…In contrast to our findings on CXCR2 surface level, our study fails to demonstrate the changes of CD64 and CCR2 surface levels as sepsis-related. CD64 and CCR2 receptors are not constitutively expressed on neutrophils at resting state (15,25); however, earlier studies showed that CD64 and CCR2 surface levels were increased during sepsis (3). The amount of CD64 mRNA elevates to a measurable level within 1-3 h of the inciting events leading to a significant increment of CD64 surface level within 4-6 h (13).…”

Section: Discussionmentioning

confidence: 99%

Distinguishing Sepsis From Infection by Neutrophil Dysfunction: A Promising Role of CXCR2 Surface Level

et al. 2020

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Sepsis is one of the well-established diseases with specific patterns of neutrophil dysfunctions. Previous studies demonstrated sepsis-related neutrophil dysfunctions in comparison with subjects without infection. Since sepsis and infection are recently recognized as distinctive processes, whether these neutrophil dysfunctions are associated with sepsis or infection are not known. Therefore, we longitudinally compared neutrophil functions, widely-cited as exhibiting sepsis-related changes, between patients with septic shock and infection. The surface level of cluster of differentiation 64 (CD64), C-C motif chemokine receptor 2 (CCR2), C-X-C motif chemokine receptor 2 (CXCR2); apoptosis; and NETosis were measured from peripheral blood neutrophils for seven consecutive days using flow cytometry. The between-group comparisons of neutrophil functions were made both on a day-by-day basis and as linear regression between time and measured neutrophil functions (sepsis status included as model predictors). Our study found that, among neutrophil functions studied, only CXCR2 surface level is associated with sepsis. At disease onset, CXCR2 level decrease, with a dose-response relationship with clinical severity. Its level reverts to resemble infected patients by the end of the week. The relationship between CD64 surface level, CCR2 surface level, NETosis, and sepsis are mediated through the effect of infection. Apoptosis activity between these groups are similar, hence, not sepsis-related.

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“…Neutrophils perform their effector activities after migration into peripheral tissues. Circulating CXCR1 + CXCR2 + mature neutrophils are orchestrated to tissues by gradients of CXCL1, CXCL2, CXCL8, CCL3, and CCL2 ( 26 ). Binding of these chemokines does not only guide the localization, but also activates them as demonstrated by CXCL8 that can elicit ROS production and induce L-Selectin shedding ( 27 ).…”

Section: Neutrophil Function In Health and Diseasementioning

confidence: 99%

Neutrophils in COVID-19

et al. 2021

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Strong evidence has been accumulated since the beginning of the COVID-19 pandemic that neutrophils play an important role in the pathophysiology, particularly in those with severe disease courses. While originally considered to be a rather homogeneous cell type, recent attention to neutrophils has uncovered their fascinating transcriptional and functional diversity as well as their developmental trajectories. These new findings are important to better understand the many facets of neutrophil involvement not only in COVID-19 but also many other acute or chronic inflammatory diseases, both communicable and non-communicable. Here, we highlight the observed immune deviation of neutrophils in COVID-19 and summarize several promising therapeutic attempts to precisely target neutrophils and their reactivity in patients with COVID-19.

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Multiple Roles for Chemokines in Neutrophil Biology

Cited by 165 publications

References 98 publications

Neutrophils Return to Bloodstream Through the Brain Blood Vessel After Crosstalk With Microglia During LPS-Induced Neuroinflammation

Neutrophils Return to Bloodstream Through the Brain Blood Vessel After Crosstalk With Microglia During LPS-Induced Neuroinflammation

Distinguishing Sepsis From Infection by Neutrophil Dysfunction: A Promising Role of CXCR2 Surface Level

Neutrophils in COVID-19

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