Stroke Alters Respiratory Burst in Neutrophils and Monocytes

Ruhnau, Johanna; Schulze, Karsten; Gaida, Bernadette; Langner, Sönke; Kessler, Christof; Bröker, Barbara M.; Dressel, Alexander; Vogelgesang, Antje

doi:10.1161/strokeaha.113.003342

Cited by 49 publications

(62 citation statements)

References 29 publications

(23 reference statements)

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“…Our results clearly demonstrated that neonates showed less formation of NET than adult controls. In controls, percentages of NET formation were comparable to those of earlier published data of our [9] as well as another group [20]. …”

Section: Discussionsupporting

confidence: 90%

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Less Neutrophil Extracellular Trap Formation in Term Newborns than in Adults

Lipp¹,

Ruhnau

Lange³

et al. 2016

Neonatology

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Background: Newborns are prone to infections, which are independent predictors of neonatal mortality and morbidity. Neutrophil extracellular traps (NETs) are structures composed of chromatin and antimicrobial molecules that capture and kill pathogens. NETs may play an important role in the innate immune system and, thus, might be associated with impaired neonatal immune function. Objectives: This study aimed to compare NET formation between term neonates and healthy adults. We additionally investigated the effects of gestational age, birth weight, mode of delivery, gender, and perinatal infections. Methods: We collected cord blood from 57 term infants (mean gestational age, 39.1 weeks) and 9 late preterm infants (35 weeks), and peripheral blood from 18 healthy adult donors. Neutrophils were isolated, and then NET formation was induced using three different stimulants: N-formylmethionine-leucyl-phenylalanine, phorbol 12-myristate 13-acetate (PMA), or lipopolysaccharide. NETs were immunohistochemically stained and analyzed with regard to NET percentage and NET area. Results: With all three stimuli, healthy term infants showed a lower NET percentage than the adult control group (p < 0.0001 each). The groups also differed in NET area, but the significance level was lower. Following PMA stimulation, we observed greater reductions in NET percentage and NET area in preterm than term infants. Conclusions: The lower NET formation observed in term infants compared to adults likely contributes to the reduced neonatal immune response. NET formation appeared to be even further decreased in late preterm neonates. There remains a need for further investigations of NET formation in more immature preterm infants.

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Section: Discussionsupporting

confidence: 90%

“…Acquired defects in neutrophil function have been detected in cases of sepsis and traumatic brain injury. Additionally, elderly people and patients suffering from ischemic stroke injury seem to show reduced NETs [8,9]. …”

Section: Introductionmentioning

confidence: 99%

Less Neutrophil Extracellular Trap Formation in Term Newborns than in Adults

Lipp¹,

Ruhnau

Lange³

et al. 2016

Neonatology

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“…In ischemic stroke, impairment of respiratory burst caused by circulating neutrophils and monocytes has also been observed. Additionally, stroke-induced neutrophil alterations are associated with the catecholamine response [27]. …”

Section: Systemic Immunosuppressionmentioning

confidence: 99%

Immunomodulation after ischemic stroke: potential mechanisms and implications for therapy

et al. 2016

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Brain injuries are often associated with intensive care admissions, and carry high morbidity and mortality rates. Ischemic stroke is one of the most frequent causes of injury to the central nervous system. It is now increasingly clear that human stroke causes multi-organ systemic disease. Brain inflammation may lead to opposing local and systemic effects. Suppression of systemic immunity by the nervous system could protect the brain from additional inflammatory damage; however, it may increase the susceptibility to infection. Pneumonia and urinary tract infection are the most common complications occurring in patients after stroke. The mechanisms involved in lung-brain interactions are still unknown, but some studies have suggested that inhibition of the cholinergic anti-inflammatory pathway and release of glucocorticoids, catecholamines, and damage-associated molecular patterns (DAMPs) are among the pathophysiological mechanisms involved in communication from the ischemic brain to the lungs after stroke. This review describes the modifications in local and systemic immunity that occur after stroke, outlines mechanisms of stroke-induced immunosuppression and their role in pneumonia, and highlights potential therapeutic targets to reduce post-stroke complications. Despite significant advances towards a better understanding of the pathophysiology of ischemic stroke-induced immunosuppression and stroke-associated pneumonia (SAP) in recent years, many unanswered questions remain. The true incidence and outcomes of SAP, especially in intensive care unit settings, have yet to be determined, as has the full extent of stroke-induced immunosuppression and its clinical implications.

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“…As rapid responders to stroke, neutrophils contribute to monocyte recruitment into CNS cells [21] and also participate in phagocytosis, as well as being phenotypically and functionally dependent upon chemokine and cytokine concentrations (tumor necrosis factor-alpha and interferon-gamma) [22]. After stroke, the antibacterial actions of neutrophils and monocytes are subsumed to phagocytic activity [23], thus priming them for the removal of necrotic CNS tissue rather than combating peripheral infection, potentially also contributing to the depressed immune responses and infections observed after ischemia. A prior study also identified higher NLR to be a maker of mortality and function in patients with intracerebral hemorrhage [24].…”

Section: Discussionmentioning

confidence: 99%

Peripheral Immune Cell Counts and Advanced Imaging as Biomarkers of Stroke Outcome

Pagram

Bivard

Lincz

et al. 2016

Cerebrovasc Dis Extra

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Introduction: Circulating neutrophil and lymphocyte levels may be modifiable outcome predictors of ischemic stroke. We sought to compare these immune cell parameters with advanced imaging assessment and the 90-day clinical outcome. Methods: We used a retrospectively collected cohort of consecutive ischemic stroke patients presenting within 4.5 h of symptom onset who had acute CT perfusion and routine blood collection before treatment with intravenous thrombolysis and 24-hour MRI scanning at the John Hunter Hospital. Full blood counts were performed acutely at 24 h and 7 days. Patient outcomes were assed at 90 days after stroke with the modified Rankin Scale (mRS). Results: Overall, 142 patients were assessed during the study period. Patients with a poor outcome (mRS 3-6) had increased neutrophils (44% increase, p = 0.016), decreased lymphocytes (7% decrease, p = 0.491) and an increased lymphocyte-to-neutrophil ratio (196% increase, p < 0.001). Patients with good outcomes (mRS 0-2) did not have significant changes in their full blood counts. There was no relationship between the neutrophil count at 24 h and penumbral volume (r² = 0.217, p = 0.212), reperfusion (r² = 0.111, p = 0.085), or core growth (r² = 0.297, p = 0.107). A backward multivariate analysis containing the 24-hour core volume and 24-hour neutrophil count was strongly related to the 3-month outcome (r² = 0.477, area under the curve = 0.902, p < 0.001). Conclusions: Peripheral neutrophils have potential as a biomarker of outcome when used in conjunction with advanced imaging. Peripherally measured neutrophil counts change significantly over time after stroke and may be potential targets for immunomodulatory therapy in patients with a severe stroke or a large infarct volume.

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Stroke Alters Respiratory Burst in Neutrophils and Monocytes

Cited by 49 publications

References 29 publications

Less Neutrophil Extracellular Trap Formation in Term Newborns than in Adults

Less Neutrophil Extracellular Trap Formation in Term Newborns than in Adults

Immunomodulation after ischemic stroke: potential mechanisms and implications for therapy

Peripheral Immune Cell Counts and Advanced Imaging as Biomarkers of Stroke Outcome

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