• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• neurologie

• MeSH
• autoprotilátky MeSH
• diferenciální diagnóza MeSH
• glomerulonefritida imunologie   klasifikace   MeSH
• lidé MeSH
• neutrofily MeSH
• vaskulitida imunologie   klasifikace   MeSH
• Check Tag
• lidé MeSH

• MeSH
• alkalická fosfatasa MeSH
• diabetes mellitus 1. typu enzymologie   krev   MeSH
• dítě MeSH
• hemoglobiny MeSH
• lidé MeSH
• neutrofily enzymologie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH

Neutrophils play a Janus-faced role in the complex landscape of cancer pathogenesis and immunotherapy. As immune defense cells, neutrophils release toxic substances, including reactive oxygen species and matrix metalloproteinase 9, within the tumor microenvironment. They also modulate the expression of tumor necrosis factor-related apoptosis-inducing ligand and Fas ligand, augmenting their capacity to induce tumor cell apoptosis. Their involvement in antitumor immune regulation synergistically activates a network of immune cells, bolstering anticancer effects. Paradoxically, neutrophils can succumb to the influence of tumors, triggering signaling cascades such as JAK/STAT, which deactivate the immune system network, thereby promoting immune evasion by malignant cells. Additionally, neutrophil granular constituents, such as neutrophil elastase and vascular endothelial growth factor, intricately fuel tumor cell proliferation, metastasis, and angiogenesis. Understanding the mechanisms that guide neutrophils to collaborate with other immune cells for comprehensive tumor eradication is crucial to enhancing the efficacy of cancer therapeutics. In this review, we illuminate the underlying mechanisms governing neutrophil-mediated support or inhibition of tumor progression, with a particular focus on elucidating the internal and external factors that influence neutrophil polarization. We provide an overview of recent advances in clinical research regarding the involvement of neutrophils in cancer therapy. Moreover, the future prospects and limitations of neutrophil research are discussed, aiming to provide fresh insights for the development of innovative cancer treatment strategies targeting neutrophils.

• MeSH
• imunoterapie * metody   MeSH
• lidé MeSH
• nádorové mikroprostředí * imunologie   MeSH
• nádory * imunologie   terapie   metabolismus   patologie   MeSH
• neutrofily * imunologie   metabolismus   MeSH
• signální transdukce MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

• MeSH
• akridiny MeSH
• fagocyty imunologie   MeSH
• kyslík metabolismus   MeSH
• NADP MeSH
• neutrofily MeSH

From the beginning of 2020, an urgent need to understand the pathophysiology of SARS-CoV-2 disease (COVID-19), much of which is due to dysbalanced immune responses, resonates across the world. COVID-19-associated neutrophilia, increased neutrophil-to-lymphocyte ratio, aberrant neutrophil activation, and infiltration of neutrophils into lungs suggest that neutrophils are important players in the disease immunopathology. The main objective of this study was to assess the phenotypic and functional characteristics of neutrophils in COVID-19 patients, with particular focus on the interaction between neutrophils and T cells. We hypothesize that the altered functional characteristics of COVID-19 patient-derived neutrophils result in skewed Th1/Th17 adaptive immune response, thus contributing to disease pathology. The expansion of G-MDSC and immature forms of neutrophils was shown in the COVID-19 patients. In the COVID-19 neutrophil/T cell cocultures, neutrophils caused a strong polarity shift toward Th17, and, conversely, a reduction of IFNγ-producing Th1 cells. The Th17 promotion was NOS dependent. Neutrophils, the known modulators of adaptive immunity, skew the polarization of T cells toward the Th17 promotion and Th1 suppression in COVID-19 patients, contributing to the discoordinated orchestration of immune response against SARS-CoV-2. As IL-17 and other Th17-related cytokines have previously been shown to correlate with the disease severity, we suggest that targeting neutrophils and/or Th17 represents a potentially beneficial therapeutic strategy for severe COVID-19 patients.

• MeSH
• aktivace neutrofilů * MeSH
• buňky Th17 imunologie   patologie   MeSH
• COVID-19 imunologie   patologie   MeSH
• interleukin-17 imunologie   MeSH
• lidé MeSH
• neutrofily imunologie   patologie   MeSH
• SARS-CoV-2 imunologie   MeSH
• Th1 buňky imunologie   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

V práci je popsána luminometrická analýza respiračního vzplanutí neutrofilů v mikrotitračníchdestičkách. Byla analyzována chemiluminiscence neutrofilů v malých objemech plné krve a v tzv.buffy coatu (plazma s leukocyty po odstranění erytrocytů dextranovou sedimentací). K vyvolánírespiračního vzplanutí byly použity 4 typy aktivátorů – opsonizovaný zymosan, forbolmyristátacetát, N-formyl-Met-Leu-Phe a vápníkový ionofor A23187. Bylo zjištěno, že kinetika chemiluminiscenční odpovědi neutrofilů v plné krvi a v buffy coatu je velmi podobná pro jednotlivé typy aktivátorů, i když chemiluminiscenční aktivita plné krve byla vždy nižší v porovnání s buffy coatem. Tobylo pravděpodobně způsobeno zvýšenou expresí buněčných receptorů v důsledku separační procedury na straně jedné a zhášecími vlastnostmi erytrocytů (hemoglobinu) na straně druhé. Zezjištěných výsledků vyplývá, že luminometrická analýza v mikrotitračních destičkách je spolehlivým nástrojem pro měření respiračního vzplanutí neutrofilů, přičemž je nutné preferovat měřenív plné krvi.

The authors describe luminometric analysis of neutrophil respiratory burst in microtitre plates.They analyzed the neutrophil luminescence in small volumes of whole blood and in the so-calledbuffy coat (plasma with leucocytes after removal of erythrocytes by dextran sedimentation).To produce respiratory burst four types of activators were used: opsonized zymosan, phorbolmyristate acetate, N-formyl-Met-Leu-Phe and calcium ionophore A23187. It was revealed that thechemiluminescence response of neutrophils in whole blood and in the buffy coat is very similar indifferent types of activators, although the chemiluminescence activity of whole blood was alwayslower as compared with the buffy coat. This was probably due to an increased expression of cellreceptors as a result of the separation procedure on the one hand and quenching properties oferythrocytes (haemoglobin) on the other hand. From the assembled results ensues that luminometric analysis in microtitre plates is a reliable protocol for assessment of the neutrophil respiratoryburst, whereby assessment in whole blood should be preferred.

• MeSH
• lidé MeSH
• luminiscence MeSH
• neutrofily imunologie   MeSH
• respirační vzplanutí účinky léků   MeSH
• Check Tag
• lidé MeSH

STAT1 gain-of-function (GOF) mutations cause an inborn error of immunity with diverse phenotype ranging from chronic mucocutaneous candidiasis (CMC) to various non-infectious manifestations, the most precarious of which are autoimmunity and vascular complications. The pathogenesis centers around Th17 failure but is far from being understood. We hypothesized that neutrophils, whose functions have not been explored in the context of STAT1 GOF CMC yet, might be involved in the associated immunodysregulatory and vascular pathology. In a cohort of ten patients, we demonstrate that STAT1 GOF human ex-vivo peripheral blood neutrophils are immature and highly activated; have strong propensity for degranulation, NETosis, and platelet-neutrophil aggregation; and display marked inflammatory bias. STAT1 GOF neutrophils exhibit increased basal STAT1 phosphorylation and expression of IFN stimulated genes, but contrary to other immune cells, STAT1 GOF neutrophils do not display hyperphosphorylation of STAT1 molecule upon stimulation with IFNs. The patient treatment with JAKinib ruxolitinib does not ameliorate the observed neutrophil aberrations. To our knowledge, this is the first work describing features of peripheral neutrophils in STAT1 GOF CMC. The presented data suggest that neutrophils may contribute to the immune pathophysiology of the STAT1 GOF CMC.

• MeSH
• aktivační mutace * MeSH
• autoimunita MeSH
• fenotyp MeSH
• fosforylace MeSH
• kandidóza chronická mukokutánní * farmakoterapie   genetika   MeSH
• lidé MeSH
• neutrofily metabolismus   MeSH
• transkripční faktor STAT1 * metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Polymorphonuclear neutrophils (PMNs) play a key role in host defense. However, their massive accumulation at the site of inflammation can delay regenerative healing processes and can initiate pathological inflammatory processes. Thus, the efficient clearance of PMNs mediated by the induction of regulated cell death is a key process preventing the development of these pathological conditions. Myeloperoxidase (MPO), a highly abundant enzyme in PMN granules, primarily connected with PMN defense machinery, is suggested to play a role in PMN-regulated cell death. However, the contribution of MPO to the mechanisms of PMN cell death remains incompletely characterized. Herein, the process of the cell death of mouse PMNs induced by three different stimuli - phorbol 12-myristate 13-acetate (PMA), opsonized streptococcus (OST), and N-formyl-met-leu-phe (fMLP) - was investigated. MPO-deficient PMNs revealed a significantly decreased rate of cell death characterized by phosphatidylserine surface exposure and cell membrane permeabilization. An inhibitor of MPO activity, 4-aminobenzoic acid hydrazide, did not exhibit a significant effect on PMA-induced cell death compared to MPO deficiency. Interestingly, only the limited activation of markers related to apoptotic cell death was observed (e.g. caspase 8 activation, Bax expression) and they mostly did not correspond to phosphatidylserine surface exposure. Furthermore, a marker characterizing autophagy, cleavage of LC3 protein, as well as histone H3 citrullination and its surface expression was observed. Collectively, the data show the ability of MPO to modulate the life span of PMNs primarily through the potentiation of cell membrane permeabilization and phosphatidylserine surface exposure.

• MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• neutrofily metabolismus   patologie   MeSH
• peroxidasa nedostatek   metabolismus   MeSH
• regulovaná buněčná smrt MeSH
• zánět metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Severe influenza infection has no effective treatment available. One of the key barriers to developing host-directed therapy is a lack of reliable prognostic factors needed to guide such therapy. Here, we use a network analysis approach to identify host factors associated with severe influenza and fatal outcome. In influenza patients with moderate-to-severe diseases, we uncover a complex landscape of immunological pathways, with the main changes occurring in pathways related to circulating neutrophils. Patients with severe disease display excessive neutrophil extracellular traps formation, neutrophil-inflammation and delayed apoptosis, all of which have been associated with fatal outcome in animal models. Excessive neutrophil activation correlates with worsening oxygenation impairment and predicted fatal outcome (AUROC 0.817-0.898). These findings provide new evidence that neutrophil-dominated host response is associated with poor outcomes. Measuring neutrophil-related changes may improve risk stratification and patient selection, a critical first step in developing host-directed immune therapy.

• MeSH
• aktivace neutrofilů imunologie   MeSH
• buněčný cyklus imunologie   MeSH
• chřipka lidská imunologie   mortalita   patologie   MeSH
• exprese genu genetika   MeSH
• extracelulární pasti imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• neutrofily imunologie   MeSH
• plíce imunologie   MeSH
• prospektivní studie MeSH
• respirační insuficience mortalita   patologie   virologie   MeSH
• umělé dýchání MeSH
• virus chřipky A, podtyp H1N1 imunologie   izolace a purifikace   MeSH
• virus chřipky A, podtyp H3N2 imunologie   izolace a purifikace   MeSH
• virus chřipky B imunologie   izolace a purifikace   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH