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Cell Reports Sep 2023Secondary infection in patients with sepsis triggers a new wave of inflammatory response, which aggravates organ injury and increases mortality. Trained immunity boosts...
Secondary infection in patients with sepsis triggers a new wave of inflammatory response, which aggravates organ injury and increases mortality. Trained immunity boosts a potent and nonspecific response to the secondary challenge and has been considered beneficial for the host. Here, using a murine model of polymicrobial infection, we find that the primary infection reprograms granulocytes to boost enhanced inflammatory responses to the secondary infection, including the excessive production of inflammatory cytokines, respiratory burst, and augmented phagocytosis capacity. However, these reprogramed granulocytes exhibit "non-classic" characteristics of innate immune memory. Two mechanisms are independently involved in the innate immune memory of granulocytes: a metabolic shift in favor of glycolysis and fatty acid synthesis and chromatin remodeling leading to the transcriptional inactivity of genes encoding inhibitors of TLR4-initiated signaling pathways. Counteracting the deleterious effects of stressed granulocytes on anti-infection immunity might provide a strategy to fight secondary infections during sepsis.
Topics: Humans; Animals; Mice; Trained Immunity; Coinfection; Granulocytes; Sepsis; Cytokines
PubMed: 37643085
DOI: 10.1016/j.celrep.2023.113044 -
Pharmacological Research Jul 2020The average respiration rate for an adult is 12-20 breaths per minute, which constantly exposes the lungs to allergens and harmful particles. As a result, respiratory... (Review)
Review
The average respiration rate for an adult is 12-20 breaths per minute, which constantly exposes the lungs to allergens and harmful particles. As a result, respiratory diseases, which includes asthma, chronic obstructive pulmonary disease (COPD) and acute lower respiratory tract infections (LTRI), are a major cause of death worldwide. Although asthma, COPD and LTRI are distinctly different diseases with separate mechanisms of disease progression, they do share a common feature - airway inflammation with intense recruitment and activation of granulocytes and mast cells. Neutrophils, eosinophils, basophils, and mast cells are crucial players in host defense against pathogens and maintenance of lung homeostasis. Upon contact with harmful particles, part of the pulmonary defense mechanism is to recruit these cells into the airways. Despite their protective nature, overactivation or accumulation of granulocytes and mast cells in the lungs results in unwanted chronic airway inflammation and damage. As such, understanding the bright and the dark side of these leukocytes in lung physiology paves the way for the development of therapies targeting this important mechanism of disease. Here we discuss the role of granulocytes in respiratory diseases and summarize therapeutic strategies focused on granulocyte recruitment and activation in the lungs.
Topics: Animals; Chemotaxis, Leukocyte; Granulocytes; Humans; Inflammation Mediators; Molecular Targeted Therapy; Phenotype; Respiratory System; Respiratory System Agents; Respiratory Tract Diseases; Signal Transduction
PubMed: 32380052
DOI: 10.1016/j.phrs.2020.104881 -
Lakartidningen Mar 2018There are no randomized controlled trials proving the clinical benefit of granulocyte transfusions. However, clinical experience and a number of case studies suggest... (Review)
Review
There are no randomized controlled trials proving the clinical benefit of granulocyte transfusions. However, clinical experience and a number of case studies suggest that granulocyte transfusions may be life-saving in certain situations. In our opinion granulocyte transfusions should be considered for patients with profound neutropenia and severe, life-threatening infection not responding to antibiotic or antifungal therapy. Since the clinical effect seems to be dose-dependent, the granulocyte concentrate should contain a large number of cells, which usually means that the donor should be mobilized with steroids and G-CSF. Regular blood donors as well as relatives to the patient can be used for granulocyte donations with apheresis technique after information of the process. Granulocyte transfusion should be given daily as long as the indication remains. The clinical efficacy of the transfusions should be evaluated daily.
Topics: Critical Illness; Donor Selection; Granulocytes; Humans; Infections; Leukocyte Transfusion; Neutropenia; Procedures and Techniques Utilization
PubMed: 29558012
DOI: No ID Found -
Seminars in Immunopathology Jun 2021It is now becoming clear that neutrophils and eosinophils are heterogeneous cells with potentially multiple subsets in health and disease. With greater marker coverage... (Review)
Review
It is now becoming clear that neutrophils and eosinophils are heterogeneous cells with potentially multiple subsets in health and disease. With greater marker coverage by multi-color flow cytometry and single-cell level sequencing of granulocyte populations, novel phenotypes of these cells began to emerge. Intriguingly, many newly described subsets blend distinctions between classical myeloid lineage phenotypes, which are especially true for tissue resident or recruited cells in contexts of inflammation and disease. This includes reports of neutrophils with features of eosinophils, monocytes and dendritic cells, and eosinophil subsets expressing neutrophil markers. Moreover, novel studies show the ability of immature neutrophils to transdifferentiate into mature cells belonging to other myeloid lineages (eosinophils, monocytes/macrophages). In this review, we summarize novel findings in this exciting research frontier and shed light on potential processes driving the plasticity and heterogeneity of granulocyte subsets. Specifically, we discuss the hematopoietic flexibility of granulocyte precursors in bone marrow and the adaptation of myeloid cells to local tissue microenvironments. The understanding of such intermediate and developmental phenotypes is very important, as it can teach us about origins of functionally distinct myeloid cells during inflammation, and explain reasons for successes and failures of biologics targeting terminally differentiated granulocytes.
Topics: Bone Marrow Cells; Cell Differentiation; Eosinophils; Humans; Monocytes; Myeloid Cells; Neutrophils
PubMed: 34009400
DOI: 10.1007/s00281-021-00862-z -
Journal of Translational Medicine Nov 2015Bacterial and fungal infections continue to pose a major clinical challenge in patients with prolonged severe neutropenia after chemotherapy or hematopoietic stem cell... (Review)
Review
Bacterial and fungal infections continue to pose a major clinical challenge in patients with prolonged severe neutropenia after chemotherapy or hematopoietic stem cell transplantation (HSCT). With the advent of granulocyte colony-stimulating factor (G-CSF) to mobilize neutrophils in healthy donors, granulocyte transfusions have been broadly used to prevent and/or treat life-threatening infections in patients with severe febrile neutropenia and/or neutrophil dysfunction. Although the results of randomized controlled trials are inconclusive, there are suggestions from pilot and retrospective studies that granulocyte transfusions may benefit selected categories of patients. We will critically appraise the evidence related to the use of therapeutic granulocyte transfusions in children and adults, highlighting current controversies in the field and discussing complementary approaches to modulate phagocyte function in the host.
Topics: Adult; Blood Component Transfusion; Child; Cytokines; Granulocytes; Hematologic Neoplasms; Humans; Randomized Controlled Trials as Topic
PubMed: 26572736
DOI: 10.1186/s12967-015-0724-5 -
British Journal of Haematology May 2017Granulocyte transfusions have a long history of being used in patients with neutropenia or neutrophil dysfunction to prevent and treat invasive fungal infections.... (Review)
Review
Granulocyte transfusions have a long history of being used in patients with neutropenia or neutrophil dysfunction to prevent and treat invasive fungal infections. However, there are limited and conflicting data concerning its clinical effectiveness, considerable variations in current granulocyte transfusion practices, and uncertainties about its benefit as an adjunct to modern antifungal therapy. In this review, we provide an overview on granulocyte transfusions and summarize the evidence on their role in the prevention and treatment of invasive fungal infections.
Topics: Donor Selection; Evidence-Based Medicine; Granulocytes; Humans; Invasive Fungal Infections; Leukocyte Transfusion; Neutrophils
PubMed: 28295178
DOI: 10.1111/bjh.14597 -
International Journal of Molecular... Apr 2021Colorectal cancer (CRC) is one of the most common malignancy and cause of cancer death worldwide, and it still remains a therapeutic challenge for western medicine.... (Review)
Review
Colorectal cancer (CRC) is one of the most common malignancy and cause of cancer death worldwide, and it still remains a therapeutic challenge for western medicine. There is strong evidence that, in addition to genetic predispositions, environmental factors have also a substantial impact in CRC development. The risk of CRC is attributed, among others to dietary habits, alcohol consumption, whereas physical activity, food containing dietary fiber, dairy products, and calcium supplements have a protective effect. Despite progress in the available therapies, surgery remains a basic treatment option for CRC. Implementation of additional methods of treatment such as chemo- and/or targeted immunotherapy, improved survival rates, however, the results are still far from satisfactory. One of the reasons may be the lack of deeper understanding of the interactions between the tumor and different types of cells, including tumor infiltrating granulocytes. While the role of neutrophils is quite well explored in many cancers, role of eosinophils and basophils is often underestimated. As part of this review, we focused on the function of different granulocyte subsets in CRC, emphasizing the beneficial role of eosinophils and basophils, as well as dichotomic mode of neutrophils action. In addition, we addressed the current knowledge on cells of granulocyte origin, specifically granulocytic myeloid derived suppressor cells (Gr-MDSCs) and their role in development and progression of CRC.
Topics: Basophils; Colorectal Neoplasms; Eosinophils; Humans; Myeloid-Derived Suppressor Cells; Neutrophils
PubMed: 33917620
DOI: 10.3390/ijms22073801 -
International Journal of Molecular... Jun 2020Over the years of evolution, thousands of different animal species have evolved. All these species require an immune system to defend themselves against invading... (Review)
Review
Over the years of evolution, thousands of different animal species have evolved. All these species require an immune system to defend themselves against invading pathogens. Nevertheless, the immune systems of different species are obviously counteracting against the same pathogen with different efficiency. Therefore, the question arises if the process that was leading to the clades of vertebrates in the animal kingdom-namely mammals, birds, amphibians, reptiles, and fish-was also leading to different functions of immune cells. One cell type of the innate immune system that is transmigrating as first line of defense in infected tissue and counteracts against pathogens is the neutrophil granulocyte. During the host-pathogen interaction they can undergo phagocytosis, apoptosis, degranulation, and form neutrophil extracellular traps (NETs). In this review, we summarize a wide spectrum of information about neutrophils in humans and animals, with a focus on vertebrates. Special attention is kept on the development, morphology, composition, and functions of these cells, but also on dysfunctions and options for cell culture or storage.
Topics: Animals; Biological Evolution; Evolution, Molecular; Extracellular Traps; Granulocytes; Host-Pathogen Interactions; Humans; Immunity, Innate; Neutrophils; Phagocytosis
PubMed: 32630520
DOI: 10.3390/ijms21124523 -
Biology of Blood and Marrow... Dec 2017Granulocyte transfusions (GTs) are seldom used as a life-saving therapy for neutropenic patients with severe infections. Despite compelling evidence of GT efficacy in... (Review)
Review
Granulocyte transfusions (GTs) are seldom used as a life-saving therapy for neutropenic patients with severe infections. Despite compelling evidence of GT efficacy in retrospective and prospective case series, no study has been successful in demonstrating a definite advantage for recipients in controlled clinical trials. This review critically revises some aspects emerging from past experience that might have weakened the evidence of GT benefits. Some specific issues relevant to the efficacy of this therapeutic approach, such as primary infection, delivered doses and schedules, and immunologic effects of GTs, are discussed. Importantly, the awareness of biologic effects accompanying the transfusion of neutrophils might support their use at standardized doses and may definitely convey significant advantages to the recipient patients.
Topics: Cell- and Tissue-Based Therapy; Granulocytes; Humans; Infections; Neutropenia; Neutrophils; Treatment Outcome
PubMed: 28797785
DOI: 10.1016/j.bbmt.2017.07.029 -
Journal of Neurochemistry Aug 2017Nicotinic acetylcholine receptors (nAChRs) are pentameric cation channels expressed in the mammalian CNS, in the peripheral nervous system, and in skeletal muscle.... (Review)
Review
Nicotinic acetylcholine receptors (nAChRs) are pentameric cation channels expressed in the mammalian CNS, in the peripheral nervous system, and in skeletal muscle. Neuronal-type nAChRs are also found in several non-neuronal cell types, including leukocytes. Granulocytes are a subtype of leukocytes that include basophils, eosinophils, and neutrophils. Granulocytes, also known as polymorphonuclear leukocytes, are characterized by their ability to produce, store, and release compounds from intracellular granules. Granulocytes are the most abundant type of leukocyte circulating in the peripheral blood. Granulocyte abundance, nAChR expression, and nAChR upregulation following chronic nicotine administration makes granulocytes interesting models for identifying protein markers of nicotine exposure. Nicotinic receptor subunits and several non-nAChR proteins have been identified as protein markers of granulocyte nicotine exposure. We review methods to isolate granulocytes from human tissue, summarize present data about the expression of nAChRs in the three granulocyte cell types (basophils, eosinophils, and neutrophils), describe current knowledge of the effects of nicotine exposure on human granulocyte protein expression, and highlight areas of interest for future investigation. This is an article for the special issue XVth International Symposium on Cholinergic Mechanisms.
Topics: Animals; Granulocytes; Humans; Nicotine; Nicotinic Agonists; Pyridines; RNA, Messenger; Receptors, Nicotinic
PubMed: 28791704
DOI: 10.1111/jnc.14010