8 results on '"Leenen, Luke P.H."'
Search Results
2. Intracellular Penetration and Effects of Antibiotics on Staphylococcus aureus Inside Human Neutrophils: A Comprehensive Review.
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Bongers, Suzanne, Hellebrekers, Pien, Leenen, Luke P.H., Koenderman, Leo, and Hietbrink, Falco
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STAPHYLOCOCCUS aureus ,NEUTROPHILS ,ANTIBIOTICS ,INTRACELLULAR pathogens ,OXAZOLIDINONES - Abstract
Neutrophils are important assets in defense against invading bacteria like staphylococci. However, (dysfunctioning) neutrophils can also serve as reservoir for pathogens that are able to survive inside the cellular environment. Staphylococcus aureus is a notorious facultative intracellular pathogen. Most vulnerable for neutrophil dysfunction and intracellular infection are immune-deficient patients or, as has recently been described, severely injured patients. These dysfunctional neutrophils can become hide-out spots or "Trojan horses" for S. aureus. This location offers protection to bacteria from most antibiotics and allows transportation of bacteria throughout the body inside moving neutrophils. When neutrophils die, these bacteria are released at different locations. In this review, we therefore focus on the capacity of several groups of antibiotics to enter human neutrophils, kill intracellular S. aureus and affect neutrophil function. We provide an overview of intracellular capacity of available antibiotics to aid in clinical decision making. In conclusion, quinolones, rifamycins and sulfamethoxazole-trimethoprim seem very effective against intracellular S. aureus in human neutrophils. Oxazolidinones, macrolides and lincosamides also exert intracellular antibiotic activity. Despite that the reviewed data are predominantly of in vitro origin, these findings should be taken into account when intracellular infection is suspected, as can be the case in severely injured patients. [ABSTRACT FROM AUTHOR]
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- 2019
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3. Instant intra-operative neutropenia despite the emergence of banded (CD16dim/CD62Lbright) neutrophils in peripheral blood - An observational study during extensive trauma-surgery in pigs.
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Teuben, Michel, Heeres, Marjolein, Blokhuis, Taco, Hollman, Arne, Vrisekoop, Nienke, Tan, Edward, Pfeifer, Roman, Pape, Hans-Christoph, Koenderman, Leo, and Leenen, Luke P.H.
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NEUTROPHILS , *TRAUMA surgery , *NEUTROPENIA , *INJURY complications , *SCIENTIFIC observation , *IMMUNOREGULATION , *EARLY ambulation (Rehabilitation) , *FLOW cytometry , *ANIMAL experimentation , *SWINE , *ANTIGENS - Abstract
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 (CD16dim/CD62Lbright) neutrophils in peripheral blood.Material and Methods: A standardized extensive thoraco-abdominal porcine trauma surgery model was utilized, and 12 animals were included. Blood was collected at defined timepoints and neutrophil numbers and subtypes were studied by flowcytometry. Neutrophil subtypes were identified by differences in cell surface expression levels of CD16 (FcγRIII) and CD62L (L-selectin). Porcine neutrophil subtypes were further characterized after flow sorting.Results: Eleven animals survived the 3-hour surgical protocol. Neutrophil numbers dropped significantly from a mean of 8,6 ± 3,5 × 106 to 2,4 ± 1,8 × 106 cells/ml during 180 min, (p<0.001). Simultaneously, the blood PMN population became increasingly heterogeneous due to the appearance of new neutrophil subtypes. Cell sorting experiments and cytological analysis revealed that these porcine subtypes had specific morphological characteristics, mimicking their human counterparts. At baseline, 88% ± 1 percent of circulatory PMNs comprised of mature (CD16bright/CD62Lbright) PMNs, while at 3 h the blood PMN pool consisted of 59% ± 2 percent of mature subtypes (p<0.001). Despite a marked drop in neutrophil levels during surgery, absolute and relative numbers of banded (CD16dim/CD62Lbright) neutrophils continued to rise throughout surgery.Conclusion: Standardized extensive trauma surgery was associated with instant progressive neutropenia and increased heterogeneity of the blood neutrophil pool. Furthermore, three different neutrophil subsets in peripheral porcine blood were identified over the course of surgery. Further studies should clarify their precise role in the development of early organ failure upon extensive trauma surgery. This for the first time exemplifies experimentally the time constraints and impact of damage control surgery after severe trauma. [ABSTRACT FROM AUTHOR]- Published
- 2021
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4. Neutrophils contribute to fracture healing by synthesizing fibronectin+ extracellular matrix rapidly after injury.
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Bastian, Okan W., Koenderman, Leo, Alblas, Jacqueline, Leenen, Luke P.H., and Blokhuis, Taco J.
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NEUTROPHILS , *FRACTURE healing , *FIBRONECTINS , *EXTRACELLULAR matrix , *BONE regeneration , *LEUCOCYTES , *PHYSIOLOGY , *THERAPEUTICS - Abstract
The role of inflammatory cells in bone regeneration remains unclear. We hypothesize that leukocytes contribute to fracture healing by rapidly synthesizing an “emergency extracellular matrix (ECM)” before stromal cells infiltrate the fracture hematoma (FH) and synthesize the eventual collagenous bone tissue. 53 human FHs were isolated at different time points after injury, ranging from day 0 until day 23 after trauma and stained using (immuno)histochemistry. FHs isolated within 48 h after injury contained fibronectin + ECM, which increased over time. Neutrophils within the early FHs stained positive for cellular fibronectin and neutrophil derived particles were visible within the fibronectin + ECM. Stromal cells appeared at day 5 after injury or later and collagen type I birefringent fibrils could be identified during the second week after injury. Our study suggests that neutrophils contribute to bone regeneration by synthesizing an “emergency ECM” before stromal cells infiltrate the FH and synthesize the eventual bone tissue. [ABSTRACT FROM AUTHOR]
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- 2016
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5. Penetrating thorax injury leads to mild systemic activation of neutrophils without inflammatory complications.
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Groeneveld, Kathelijne M., Hietbrink, Falco, Hardcastle, Timothy C., Warren, Brian L., Koenderman, Leo, and Leenen, Luke P.H.
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CHEST injuries , *NEUTROPHILS , *INFLAMMATION , *MORTALITY , *FLOW cytometry , *BLOOD sampling - Abstract
Abstract: Introduction: Trauma is one of the major causes of morbidity and mortality. Thoracic injuries are associated with inflammatory complications such as ARDS. The pathogenesis of this complication after pulmonary injury is incompletely understood, but neutrophils are thought to play a pivotal role. The aim of this project was to gain more insight in the role of thoracic injuries in the pathophysiological processes that link systemic neutrophil activation with inflammatory complications after trauma. Methods: In this prospective cohort study fifty-five patients with isolated penetrating thoracic injury were included at a level one Trauma Unit. Blood samples were analysed for neutrophil phenotype with the use of flowcytometry within 3h of trauma and repeated six and 24h after injury. The presence of inflammatory complications (e.g. ARDS or sepsis/septic shock) was assessed during admission, and this was related to the neutrophil phenotpe. Results: The clinical follow-up of fifty-three patients was uneventful. Only two patients developed an inflammatory complication. Within 3h after trauma, neutrophils showed a decreased expression of FcγRII (p =0.007) and FcγRIII (p =0.001) compared to healthy individuals. After 6h, expression of active FcγRII (p =0.017), C5aR (p =0.004) and CAECAM8 (p =0.043) increased, whereas L-selectin (p =0.002) decreased. After 24h also CXCR-2 (CD182) expression increased compared to healthy individuals (p =0.001). Conclusions: Penetrating thoracic trauma leads to a distinct primed activation status of circulating neutrophils within hours. In addition to activation of cells, both young and reverse migrated neutrophils are released into the circulation. This degree of systemic inflammation does not exceed a threshold of inflammation that is needed for the development of inflammatory complications like ARDS. [Copyright &y& Elsevier]
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- 2014
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6. Mechanical ventilation increases the inflammatory response induced by lung contusion.
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van Wessem, Karlijn J.P., Hennus, Marije P., van Wagenberg, Linda, Koenderman, Leo, and Leenen, Luke P.H.
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ARTIFICIAL respiration , *BLUNT trauma , *GRANULOCYTES , *BRONCHOALVEOLAR lavage , *VENTILATION , *ANIMAL models in research , *LABORATORY rats - Abstract
Abstract: Background: Posttraumatic lung contusion is common after blunt chest trauma, and patients often need ventilatory support. Lung contusion induces an inflammatory response signified by primed polymorph neutrophil granulocytes (PMNs) in blood and tissue. Mechanical ventilation (MV) can also cause an inflammatory response. The aim of this study was to develop an animal model to investigate the effect of high-volume ventilation on the inflammatory response in blunt chest trauma. Materials and methods: We assigned 23 male Sprague-Dawley rats to either MV or bilateral lung contusion followed by MV. We used three extra rats as controls. Lung contusion was induced by a blast generator, a device releasing a single pressure blast wave centered on the chest. We determined tissue and systemic inflammation by absolute PMN numbers in blood and bronchoalveolar lavage fluid (BALF), myeloperoxidase, interleukin (IL)-6, IL 1β, growth-related oncogene–KC, and IL-10 in both plasma and BALF. Results: Survival after blunt chest trauma was correlated to the distance to the blast generator. Compared with controls, both MV and blast plus MV rats showed increased systemic and pulmonary inflammation, expressed by higher PMNs, myeloperoxidase levels, and cytokine levels in both blood and BALF. Blast plus MV rats showed a higher systemic and pulmonary inflammatory response than MV rats. Conclusions: The blast generator generated reproducible blunt chest trauma in rats. Mechanical ventilation after lung contusion induced a larger overall inflammatory response than MV alone, which indicates that local damage contributes not only to local inflammation, but also to systemic inflammation. This emphasizes the importance of lung protective ventilation strategies after pulmonary contusion. [Copyright &y& Elsevier]
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- 2013
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7. Mechanical ventilation is the determining factor in inducing an inflammatory response in a hemorrhagic shock model
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van Wessem, Karlijn J.P., Hennus, Marije P., Heeres, Marjolein, Koenderman, Leo, and Leenen, Luke P.H.
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ARTIFICIAL respiration , *HEMORRHAGIC shock , *IMMUNE system , *INFLAMMATION , *GRANULOCYTES , *BRONCHOALVEOLAR lavage - Abstract
Abstract: Background: Hemorrhagic shock (HS) is known to induce an inflammatory response by activating the immune system. This response is mainly caused by primed polymorphonuclear granulocytes (PMNs). Trauma patients often require mechanical ventilation (MV), which can cause additional pulmonary and systemic inflammation. The aim of this study was to evaluate the role of MV in the development of systemic and pulmonary inflammation in a HS model in rats. Materials and methods: In male Sprague–Dawley rats, the effect of MV and HS on the systemic and pulmonary inflammatory responses was measured and compared. In five groups (control, sham, MV, HS, and MV + HS), the inflammation was measured at time point 300 min after the start of the experiment. Results: The systemic inflammatory response, expressed in absolute numbers of PMNs in blood and blood growth related oncogene (GRO-KC) levels, was significantly higher in MV rats compared with that in other groups. The pulmonary inflammatory response, expressed by PMNs in bronchoalveolar lavage fluid (BALF), BALF interleukin 6, BALF GRO-KC, and myeloperoxidase activity, was significantly higher in all ventilated rats compared with that in the controls or HS rats. There was, however, no additional effect of HS in MV as the inflammatory indices were similar in both groups. Conclusions: Our data show that HS alone has minimal effect on the development of inflammation. MV (alone or in combination with HS) is the determining factor in inducing an inflammatory response. These results emphasize the importance of local (pulmonary) ventilation-induced damage in the development of systemic inflammation. [Copyright &y& Elsevier]
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- 2013
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8. Modulation of the innate immune response after trauma visualised by a change in functional PMN phenotype
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Hietbrink, Falco, Koenderman, Leo, Althuizen, Martje, and Leenen, Luke P.H.
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IMMUNOREGULATION , *NATURAL immunity , *INJURY complications , *ADULT respiratory distress syndrome , *PHENOTYPES , *NEUTROPHILS - Abstract
Abstract: Background: Acute Respiratory Distress Syndrome (ARDS) is a frequent and severe complication after trauma, caused by an excessive inflammatory response mediated by polymorphonuclear granulocytes (PMNs). It was previously demonstrated that patients with activated PMNs in the lungs have PMNs in the peripheral circulation with a reduced active FcγRII up-regulating capacity. We tested the hypothesis that a correlation exists between the severity of inflammation and the extent of decreased responsiveness of active FcγRII on circulating PMNs, as a sign of altered immunological capacity. Methods: Fifty-two patients were included and injury severity was assessed by clinical injury severity scores and base deficit. Symptoms and signs of inflammation were recorded on a daily basis and fMLP-induced active FcγRII on PMNs was assessed by FACS analysis within 24h after injury. Results were compared with 10, age matched healthy controls. Results: The baseline PMN membrane expression of Mac-1/CD11b and active FcγRII/CD32 did not correlate with injury severity. Levels of the acute phase protein Interleukin 6 (IL-6) correlated significantly with injury severity, indicating that a range in severity of the inflammatory response was present in the studied population. A statistically significant correlation between the PMN responsiveness towards the bacterial derived peptide fMLP of active FcγRII and injury severity was demonstrated. In addition, decreasing responsiveness of active FcγRII on PMNs was found in patients who developed systemic inflammatory response syndrome (SIRS) or acute lung injury (ALI)/ARDS. Conclusions: The extent of the sustained injury and the subsequent cellular innate immune response is reflected by changes in a functional PMN phenotype of fMLP-induced active FcγRII in the peripheral blood. [Copyright &y& Elsevier]
- Published
- 2009
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