Neutrophil Dysfunction in Sepsis

Zhang, Fang; Liu, Anlei; Gao, Shuang; Ma, Shui; Guo, Shubin

doi:10.4103/0366-6999.193447

Cited by 34 publications

(33 citation statements)

References 40 publications

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“…Similar findings were seen in a previous study investigating the directional migration speed of isolated neutrophils following burn injury [ 20 ]. One explanation for the observed decrease in neutrophil migration abilities is that high levels of circulating proinflammatory cytokines early in sepsis increase levels of inducible nitric oxide which in turn may decrease neutrophil adhesion and transmigration to inflammatory sites [ 21 , 22 ]. Additionally, it has been shown that there is a significant increase in rigidity of neutrophils isolated from septic patients compared to normal controls [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Sepsis is associated with reduced spontaneous neutrophil migration velocity in human adults

et al. 2018

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Sepsis is a common and deadly complication among trauma and surgical patients. Neutrophils must mobilize to the site of infection to initiate an immediate immune response. To quantify the velocity of spontaneous migrating blood neutrophils, we utilized novel microfluidic approaches on whole blood samples from septic and healthy individuals. A prospective study at a level 1 trauma and tertiary care center was performed with peripheral blood samples collected at <12 hours, 4 days, and/or 14 days relative to study initiation. Blood samples were also collected from healthy subjects. Ex vivo spontaneous neutrophil migration was measured on 2 μl of whole blood using microfluidic devices and time-lapse imaging. For each sample, individual neutrophils were tracked to calculate mean instantaneous velocity. Forty blood samples were collected from 33 patients with sepsis, and 15 blood samples were collected from age- and gender-matched healthy, control subjects. Average age was 61 years for septic patients with a male predominance (67%). Overall, average spontaneous neutrophil migration velocity in septic samples was 16.9 μm/min, significantly lower than controls samples at 21.1 μm/min (p = 0.0135). Neutrophil velocity was reduced the greatest at <12 hours after sepsis (14.5 μm/min). Regression analysis demonstrated a significant, positive correlation between neutrophil velocity and days after sepsis (p = 0.0059). There was no significant association between neutrophil velocity and age, gender, APACHE II score, SOFA score, sepsis severity, total white blood cell count, or percentage of neutrophils. Circulating levels of the cytokines IL-6, IL-8, IL-10, MCP-1, IP-10, and TNF were additionally measured using bead-based multiplex assay and found to peak at <12 hours and be significantly increased in patients with sepsis at all three time points (<12 hours, 4 days, and 14 days after sepsis) compared to healthy subjects. In conclusion, these findings may demonstrate an impaired ability of neutrophils to respond to sites of infection during the proinflammatory phase of sepsis.

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Section: Discussionmentioning

confidence: 99%

Sepsis is associated with reduced spontaneous neutrophil migration velocity in human adults

et al. 2018

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“…The duration and degree of neutropenia underscored the increased risk of life-threatening infections. [ 14 ] Fever and neutropenia are common in patients with hematologic malignancies during chemotherapy, and approximately 10–30% of patients experience sepsis. [ 15 ] Severe neutropenia is a risk factor for an infection that occurs in acute leukemia after chemotherapy and is an important factor that affects the prognosis of infection.…”

Section: Discussionmentioning

confidence: 99%

Clinical Characteristics of Bloodstream Infections in Pediatric Acute Leukemia

Yao

Jin

2017

Chinese Medical Journal

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Background:Acute leukemia is the most common pediatric hematological malignancy. Bloodstream infections (BSIs) are severe complications in these patients during chemotherapy. This study aimed to explore the clinical presentation and etiology of BSI, as well as the common sites of infection, and to provide a basis for the rational regarding antibiotic use.Methods:We performed a retrospective chart review of all pediatric patients who had acute leukemia accompanied by a BSI in our hospital from December 2011 to September 2015. All patients were selected based on clinical presentation and had to have at least one positive blood culture for inclusion. The basic clinical characteristics, blood culture results, and antimicrobial susceptibilities were analyzed.Results:All 231 patients had a fever; of them, 12 patients continued to have a fever. Twenty-five patients had nonremitting (NR) leukemia, and 206 patients achieved complete remission (CR). Differences in the duration of fever between the NR and CR groups were significant (9.6 ± 7.9 vs. 5.1 ± 3.8 days, P = 0.016). One hundred and eighty patients had agranulocytosis. Differences in fever duration between the agranulocytosis and nonagranulocytosis groups were significant (6.2 ± 5.1 vs. 4.1 ± 2.6 days, P = 0.001). The other sites of infection in these 231 patients were the lung, mouth, digestive tract, and rectum. Blood culture comprised 2635 samples. There were 619 samples, which were positive. Of the 619 positive blood culture samples, 59.9% had Gram-negative bacteria, 39.3% had Gram-positive bacteria, and 0.8% had fungus. The primary pathogens were Pseudomonas aeruginosa, Enterobactercloacae, Escherichia coli, and Klebsiella pneumoniae. Of these 231 patients, 217 patients were cured. The effective treatment ratio was 94%.Conclusions:Gram-negative bacteria were the main pathogenic bacteria in patients with acute leukemia in our center. NR primary illness, agranulocytosis, and drug-resistant pathogenic bacteria were all risk factors for poor prognosis.

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“…While this model did not directly use bacterial challenge, it employed mixtures of cytokines important for sepsis in humans, which is defined as "life-threatening organ dysfunction caused by a dysregulated host response to infection" [70], in which neutrophilic inflammation is an important component [71]. Another antimicrobial mechanism involves the release of histone-bound DNA complexed with primary granule proteins, such as NE and myeloperoxidase (MPO), in the form of NETs [72].…”

Section: Bacterial Infectionsmentioning

confidence: 99%

Neutrophil Adaptations upon Recruitment to the Lung: New Concepts and Implications for Homeostasis and Disease

Giacalone

Margaroli

Mall

et al. 2020

IJMS

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Neutrophils have a prominent role in all human immune responses against any type of pathogen or stimulus. The lungs are a major neutrophil reservoir and neutrophilic inflammation is a primary response to both infectious and non-infectious challenges. While neutrophils are well known for their essential role in clearance of bacteria, they are also equipped with specific mechanisms to counter viruses and fungi. When these defense mechanisms become aberrantly activated in the absence of infection, this commonly results in debilitating chronic lung inflammation. Clearance of bacteria by phagocytosis is the hallmark role of neutrophils and has been studied extensively. New studies on neutrophil biology have revealed that this leukocyte subset is highly adaptable and fulfills diverse roles. Of special interest is how these adaptations can impact the outcome of an immune response in the lungs due to their potent capacity for clearing infection and causing damage to host tissue. The adaptability of neutrophils and their propensity to influence the outcome of immune responses implicates them as a much-needed target of future immunomodulatory therapies. This review highlights the recent advances elucidating the mechanisms of neutrophilic inflammation, with a focus on the lung environment due to the immense and growing public health burden of chronic lung diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD), and acute lung inflammatory diseases such as transfusion-related acute lung injury (TRALI).

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Neutrophil Dysfunction in Sepsis

Cited by 34 publications

References 40 publications

Sepsis is associated with reduced spontaneous neutrophil migration velocity in human adults

Sepsis is associated with reduced spontaneous neutrophil migration velocity in human adults

Clinical Characteristics of Bloodstream Infections in Pediatric Acute Leukemia

Neutrophil Adaptations upon Recruitment to the Lung: New Concepts and Implications for Homeostasis and Disease

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