Neutrophils in cancer: from biology to therapy.

The view of neutrophils has shifted from simple phagocytic cells, whose main function is to kill pathogens, to very complex cells that are also involved in immune regulation and tissue repair. These cells are essential for maintaining and regaining tissue homeostasis. Neutrophils can be viewed as double-edged swords in a range of situations.

Limited impact of traumatic brain injury on the post-traumatic inflammatory cellular response.

Purpose: Trauma triggers a systemic inflammatory cellular response due to tissue damage, potentially leading to a secondary immune deficiency. Trauma severity is quantified by the Injury Severity Score (ISS). Severe Traumatic Brain Injury (TBI) is associated with high ISSs due to high lethality, despite limited tissue damage.

Automated, Point-of-Care mobile flow cytometry: Bringing the laboratory to the sample.

Background: Innate effector cells are very responsive to infectious and inflammatory cues found in damaged and inflamed tissues. Their activation is a potential target to assess the state of the immune system. Unfortunately, these cells are very susceptible for ex-vivo activation, hampering accurate interpretation of flow cytometry data.

Nuclear segmentation facilitates neutrophil migration.

Neutrophils are among the fastest-moving immune cells. Their speed is critical to their function as 'first responder' cells at sites of damage or infection, and it has been postulated that the unique segmented nucleus of neutrophils functions to assist their rapid migration. Here, we tested this hypothesis by imaging primary human neutrophils traversing narrow channels in custom-designed microfluidic devices.

Visualization of the inflammatory response to injury by neutrophil phenotype categories : Neutrophil phenotypes after trauma.

Purpose: The risk of infectious complications after trauma is determined by the amount of injury-related tissue damage and the resulting inflammatory response. Recently, it became possible to measure the neutrophil phenotype in a point-of-care setting. The primary goal of this study was to investigate if immunophenotype categories based on visual recognition of neutrophil subsets are applicable to interpret the inflammatory response to trauma.

Human neutrophil kinetics: a call to revisit old evidence.

The half-life of human neutrophils is still controversial, with estimates ranging from 7-9 h to 3.75 days. This debate should be settled to understand neutrophil production in the bone marrow (BM) and the potential and limitations of emergency neutropoiesis following infection or trauma.

Longitudinal assessment of the inflammatory response: The next step in personalized medicine after severe trauma.

Infections in trauma patients are an increasing and substantial cause of morbidity, contributing to a mortality rate of 5-8% after trauma. With increased early survival rates, up to 30-50% of multitrauma patients develop an infectious complication. Trauma leads to a complex inflammatory cascade, in which neutrophils play a key role.

Neutrophils Promote Glioblastoma Tumor Cell Migration after Biopsy.

Glioblastoma is diagnosed by biopsy or, if clinically feasible, tumor resection. However, emerging evidence suggests that this surgical intervention may increase the risk of tumor cell spread. It has been hypothesized that the damage to the tumor leads to infiltration of immune cells that consequently form an environment that favors tumor cell motility.

Shift of Neutrophils From Blood to Bone Marrow Upon Extensive Experimental Trauma Surgery.

Introduction: Extensive trauma surgery evokes an immediate cellular immune response including altered circulatory neutrophil numbers. The concurrent bone marrow (BM) response however is currently unclear. We hypothesize that these BM changes include (1) a relative reduction of the bone marrow neutrophil fraction and (2) increasing heterogeneity of the bone marrow neutrophil pool due to (3) the appearance of aged/returning neutrophils from circulation into the BM-compartment.

Differential effects of short- and long-term treatment with mepolizumab on eosinophil kinetics in blood and sputum in eosinophilic asthma.

Mepolizumab (anti-IL-5) is a successful biological for treatment of T2/eosinophilic asthma by blocking the IL-5-eosinophil axis. The kinetics of human eosinophils in blood and sputum was determined to better understand the underlying mechanism(s). Pulse-chase labeling was performed with 6,6-H-glucose in patients with asthma after short term (4 days) and long term (84 days) treatment with mepolizumab (n = 10) or placebo (n = 10).

Transformation of multicolour flow cytometry data with OTflow prevents misleading multivariate analysis results and incorrect immunological conclusions.

The rapid evolution of the flow cytometry field, currently allowing the measurement of 30-50 parameters per cell, has led to a marked increase in deep multivariate information. Manual gating is insufficient to extract all this information. Therefore, multivariate analysis (MVA) methods have been developed to extract information and efficiently analyze the high-density multicolour flow cytometry (MFC) data.

Kinetics of Neutrophil Subsets in Acute, Subacute, and Chronic Inflammation.

At homeostasis the vast majority of neutrophils in the circulation expresses CD16 and CD62L within a narrow expression range, but this quickly changes in disease. Little is known regarding the changes in kinetics of neutrophils phenotypes in inflammatory conditions. During acute inflammation more heterogeneity was found, characterized by an increase in CD16 banded neutrophils.

The Systemic Immune Response in COVID-19 Is Associated with a Shift to Formyl-Peptide Unresponsive Eosinophils.

A malfunction of the innate immune response in COVID-19 is associated with eosinopenia, particularly in more severe cases. This study tested the hypothesis that this eosinopenia is COVID-19 specific and is associated with systemic activation of eosinophils. Blood of 15 healthy controls and 75 adult patients with suspected COVID-19 at the ER were included before PCR testing and analyzed by point-of-care automated flow cytometry (CD10, CD11b, CD16, and CD62L) in the absence or presence of a formyl peptide (fNLF).

Refractory neutrophils and monocytes in patients with inflammatory bowel disease after repeated bouts of prolonged exercise.

Background: Neutrophils and monocytes are key immune effector cells in inflammatory bowel disease (IBD) that is associated with chronic inflammation in the gut. Patients with stable IBD who perform exercise have significantly fewer flare-ups of the disease, but no underlying mechanism has been identified. Therefore, the aim of this study was to compare the responsiveness/refractoriness of these innate immune cells after repeated bouts of prolonged exercise in IBD patients and controls.

CD5 levels define functionally heterogeneous populations of naïve human CD4 T cells.

Studies in murine models show that subthreshold TCR interactions with self-peptide are required for thymic development and peripheral survival of naïve T cells. Recently, differences in the strength of tonic TCR interactions with self-peptide, as read-out by cell surface levels of CD5, were associated with distinct effector potentials among sorted populations of T cells in mice. However, whether CD5 can also be used to parse functional heterogeneity among human T cells is less clear.

Flow cytometric evaluation of the neutrophil compartment in COVID-19 at hospital presentation: A normal response to an abnormal situation.

Coronavirus disease 2019 (COVID-19) is a rapidly emerging pandemic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Critical COVID-19 is thought to be associated with a hyper-inflammatory process that can develop into acute respiratory distress syndrome, a critical disease normally mediated by dysfunctional neutrophils. This study tested the hypothesis whether the neutrophil compartment displays characteristics of hyperinflammation in COVID-19 patients.

An increase in CD62L neutrophils precedes the development of pulmonary embolisms in COVID-19 patients.

Objectives: A high incidence of pulmonary embolism (PE) is reported in patients with critical coronavirus disease 2019 (COVID-19). Neutrophils may contribute to this through a process referred to as immunothrombosis. The aim of this study was to investigate the occurrence of neutrophil subpopulations in blood preceding the development of COVID-19 associated PE.

Instant intra-operative neutropenia despite the emergence of banded (CD16/CD62L) neutrophils in peripheral blood - An observational study during extensive trauma-surgery in pigs.

Introduction: Deregulation of polymorphonuclear neutrophils (PMNs) is an essential step in the development of inflammatory complications upon trauma. Different neutrophil subtypes have been identified recently, however, the role of neutrophil subtypes in immunoregulation upon trauma is unclear. We hypothesize that extensive trauma surgery causes instant progressive heterogeneity of the blood neutrophil pool, and increased appearance of young (CD16/CD62L) neutrophils in peripheral blood.

Analysis of human neutrophil phenotypes as biomarker to monitor exercise-induced immune changes.

The amplitude of the innate immune response reflects the degree of physiological stress imposed by exercise load. An optimal balance of exercise intensity and duration is essential for a balanced immune system and reduces the risk of dysfunction of the immune system. Therefore, it is hypothesized that neutrophils, as key players in the innate immune system, can be used as biomarker in detecting overtraining.

Point-of-Care Analysis of Neutrophil Phenotypes: A First Step Toward Immuno-Based Precision Medicine in the Trauma ICU.

Objectives: The amount of tissue damage and the amplitude of the immune response after trauma are related to the development of infectious complications later on. Changes in the neutrophil compartment can be used as read out of the amplitude of the immune response after trauma. The study aim was to test whether 24/7 point-of-care analysis of neutrophil marker expression by automated flow cytometry can be achieved after trauma.

Multi-set Pre-processing of Multicolor Flow Cytometry Data.

Flow Cytometry is an analytical technology to simultaneously measure multiple markers per single cell. Ten thousands to millions of single cells can be measured per sample and each sample may contain a different number of cells. All samples may be bundled together, leading to a 'multi-set' structure.

New automated analysis to monitor neutrophil function point-of-care in the intensive care unit after trauma.

Background: Patients often develop infectious complications after severe trauma. No biomarkers exist that enable early identification of patients who are at risk. Neutrophils are important immune cells that combat these infections by phagocytosis and killing of pathogens.