Molecular Mechanisms Underlying Delayed Apoptosis in Neutrophils from Multiple Trauma Patients with and without Sepsis

Paunel-Görgülü, Adnana; Kirichevska, Tamara; Lögters, Tim; Windolf, Joachim; Flohé, Sascha

doi:10.2119/molmed.2011.00380

Cited by 55 publications

(52 citation statements)

References 46 publications

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“…However, following traumatic injury, their life-span is markedly increased. In line with data published within the field of burns research [15], Junger et al [6] and Paunel-Gorgulu and co-workers [49,50] have recently shown the rate of apoptosis for neutrophils isolated from TBI patients and victims of blunt/penetrating trauma respectively is significantly lower following overnight culture than that of neutrophils from uninjured controls [6,49,50].…”

Section: Apoptosissupporting

confidence: 71%

“…Thus, the balance between pro-and anti-apoptotic proteins is a critical factor in the induction of apoptosis by the intrinsic pathway. Recently, neutrophils isolated from multiply injured patients (injury severity score [ISS] > 16) were found to express significantly greater amounts of the anti-apoptotic protein myeloid cell leukaemia 1 (Mcl-1) and significantly lower levels of the proapoptotic protein Bax [50,52], a balance that would favour stabilisation of mitochondrial membrane potential and cell survival. These findings were in line with those of an earlier study, where in a rodent model of thermal injury, increased expression of the anti-apoptotic protein Bcl-xL was found in neutrophils isolated from burnt rats when compared to those from uninjured controls [53].…”

Section: Apoptosismentioning

confidence: 99%

“…Culturing neutrophils isolated from healthy volunteers overnight in the presence of serum from trauma patients has been shown to significantly prolong their life-span in vitro [50,52]. This suggests that circulating soluble factors mediate at least in part the delay in neutrophil apoptosis that occurs following injury.…”

Section: Apoptosismentioning

confidence: 99%

“…caspase-1, cyclin-dependent kinase 2 and protein kinase B) was observed and accompanied by a significant down-regulation of proteins with potential pro-apoptotic properties [19]. Such changes would promote neutrophil survival and thus may contribute to the extended half-life of neutrophils following trauma [6,49,50].…”

Section: Microrna and Proteomic Profilingmentioning

confidence: 99%

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The impact of trauma on neutrophil function

Hazeldine

Hampson

Lord

2014

Injury

103

104

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A well described consequence of traumatic injury is immune dysregulation, where an initial increase in immune activity is followed by a period of immune depression, the latter leaving hospitalised trauma patients at an increased risk of nosocomial infections. Here, we discuss the emerging role of the neutrophil, the most abundant leucocyte in human circulation and the first line of defence against microbial challenge, in the initiation and propagation of the inflammatory response to trauma. We review the findings of the most recent studies to have investigated the impact of trauma on neutrophil function and discuss how alterations in neutrophil biology are being investigated as potential biomarkers by which to predict the outcome of hospitalised trauma patients. Furthermore, with trauma-induced changes in neutrophil biology linked to the development of such post-traumatic complications as multiple organ failure and acute respiratory distress syndrome, we highlight an area of research within the field of trauma immunology that is gaining considerable interest: the manipulation of neutrophil function as a means by which to potentially improve patient outcome.

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Section: Apoptosissupporting

confidence: 71%

Section: Apoptosismentioning

confidence: 99%

Section: Apoptosismentioning

confidence: 99%

Section: Microrna and Proteomic Profilingmentioning

confidence: 99%

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The impact of trauma on neutrophil function

Hazeldine

Hampson

Lord

2014

Injury

103

104

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“…Paunel-Gorgulu et al (30) showed that the severity of sepsis correlated with reduced neutrophil apoptosis further supports the importance of neutrophil activity in the pathophysiology of sepsis, and drugs designed to target apoptotic signaling in neutrophils during sepsis may help to modulate the lifespan of neutrophils, thus preventing host tissue damage under these conditions. Furthermore, patients with septic shock who receive donor granulocytes show improvements in various biomarkers of sepsis, as well as decreased sepsis severity (31, 32).…”

Section: Discussionmentioning

confidence: 85%

Apoptotic Changes in the Early Diagnosis and Severity Determination of Neonatal Sepsis

Barseem

Helwa

2016

Iran J Pediatr

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Objectives: The aim of this study was to assess the presence of DNA damage in full-term newborns with neonatal sepsis. Methods: Sixty neonates with early onset neonatal sepsis and 45 apparently healthy controls were enrolled in the study. Screening of neonates was done using a modified clinical sepsis score and hematological scoring system, adjusted to the results of blood culture and screening tests. Complete blood count, C-reactive protein (CRP), and DNA studies were done. Results: Sepsis was likely in 41 (68.3%) patients with scores of 3 or 4 and CRP levels of 12 -48 mg/L. Sepsis was very likely in 19 (31.7%) patients with scores of ≥ 5 and CRP of 48 -96 mg/L. Sepsis was unlikely in all controls with scores of ≤ 2. The mean neutrophil count was 9700 ± 4600/µL in patients and 4230 ± 1400/µL in controls. The higher the total polymorphonuclear count and CRP level, the more severe was the sepsis. Twenty-six of 60 (43.3%) sepsis patients and 5 of 45 controls (11%) had DNA damage. There was a highly significant negative correlation between DNA damage, blood culture results, and CRP levels. Conclusions: DNA damage, demonstrated by clinical and laboratory evidence with a combination of blood cultures, CRP, and hematological scoring system results, can be used as an indicator of both the immune status of the neonate and the severity of the sepsis.

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