Regulation of L-selectin expression by trauma-relevant cytokines

Mommsen, Philipp; Barkhausen, Tanja; Hildebrand, Frank; Zeckey, Christian; Krettek, Christian; Griensven, Martijn van

doi:10.1016/j.prp.2010.12.003

Cited by 14 publications

(7 citation statements)

References 46 publications

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“…In our study, the bacterial tripeptide fMLF was used as a neutrophil stimulator ex vivo . Upon exposure to fMLF neutrophils would normally shed CD62L from their cell surface 39 , with increased levels of its soluble form present in the plasma as a result. In this study, shedding was less prominent in MODS patients than in non-MODs at all time points (Fig.…”

Section: Discussionmentioning

confidence: 99%

Machine learning for the detection of early immunological markers as predictors of multi-organ dysfunction

et al. 2019

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The immune response to major trauma has been analysed mainly within post-hospital admission settings where the inflammatory response is already underway and the early drivers of clinical outcome cannot be readily determined. Thus, there is a need to better understand the immediate immune response to injury and how this might influence important patient outcomes such as multi-organ dysfunction syndrome (MODS). In this study, we have assessed the immune response to trauma in 61 patients at three different post-injury time points (ultra-early (<=1 h), 4–12 h, 48–72 h) and analysed relationships with the development of MODS. We developed a pipeline using Absolute Shrinkage and Selection Operator and Elastic Net feature selection methods that were able to identify 3 physiological features (decrease in neutrophil CD62L and CD63 expression and monocyte CD63 expression and frequency) as possible biomarkers for MODS development. After univariate and multivariate analysis for each feature alongside a stability analysis, the addition of these 3 markers to standard clinical trauma injury severity scores yields a Generalized Liner Model (GLM) with an average Area Under the Curve value of 0.92 ± 0.06. This performance provides an 8% improvement over the Probability of Survival (PS14) outcome measure and a 13% improvement over the New Injury Severity Score (NISS) for identifying patients at risk of MODS.

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Section: Discussionmentioning

confidence: 99%

Machine learning for the detection of early immunological markers as predictors of multi-organ dysfunction

et al. 2019

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“…Stimulation with tumor necrosis factor alpha (TNF-α) has been shown to effect a significant decrease in L-selectin expression [34]. Taking the diffuse cutaneous form of SSc as a chronic inflammatory disease suggests a possible therapeutic role of a TNF-α blocker, or other biologics, or interference with the selectins or their ligands, in reducing skin damage in SSc patients through the effect of increased L-selectin expression, which can in turn be monitored by looking for increasing soluble L-selectin in the plasma of patients.…”

Section: Discussionmentioning

confidence: 99%

L-selectin and Skin Damage in Systemic Sclerosis

2012

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BackgroundL-selectin ligands are induced on the endothelium of inflammatory sites. L-selectin expression on neutrophils and monocytes may mediate the primary adhesion of these cells at sites of inflammation by mediating the leukocyte-leukocyte interactions that facilitate their recruitment. L-selectin retains functional activity in its soluble form. Levels of soluble L-selectin have been reported as both elevated and lowered in patients with systemic sclerosis (SSc). This preliminary study seeks to discern amongst these disparate results and to discover whether there is an association between L-selectin concentrations in plasma and skin damage in SSc patients.Methodology and Principal FindingsNineteen cases with limited systemic sclerosis (lSSc) and 11 cases with diffuse systemic sclerosis (dSSc) were compared on a pairwise basis to age- and sex-matched controls. Criteria of the American College of Rheumatology were used to diagnose SSc. Skin involvement was assessed using the modified Rodnan skin score (mRSS). We find no association between mRSS and plasma L-selectin concentration in lSSc cases (p = 0.9944) but a statistically significant negative correlation in dSSc cases (R2 = 73.11 per cent, p = 0.0008). The interpretation of the slope for dSSc cases is that for each increase of 100 ng/ml in soluble L-selectin concentration, the mRSS drops 4.22 (95 per cent CI: 2.29, 6.16). There was also a highly statistically significant negative correlation between sL-selectin and disease activity (p = 0.0007) and severity (p = 0.0007) in dSSc cases but not in lSSc cases (p = 0.2596, p = 0.7575, respectively).Conclusions and SignificanceNo effective treatments exist for skin damage in SSc patients. Nor is there a laboratory alternative to the modified Rodnan skin score as is the case for other organs within the body. Modulation of circulating L-selectin is a promising target for reducing skin damage in dSSc patients. Plasma levels of soluble L-selectin could serve as an outcome measure for dSSc patients in clinical trials.

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“…Recently, Mommsen and co-workers [23] found that stimulating neutrophils in vitro with tumour necrosis factoralpha (TNF-a) resulted in shedding of L-selectin, suggesting that exposure to a pro-inflammatory environment may be one explanation for the reduced expression of L-selectin post trauma.…”

Section: Surface Phenotypementioning

confidence: 99%

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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Regulation of L-selectin expression by trauma-relevant cytokines

Cited by 14 publications

References 46 publications

Machine learning for the detection of early immunological markers as predictors of multi-organ dysfunction

Machine learning for the detection of early immunological markers as predictors of multi-organ dysfunction

L-selectin and Skin Damage in Systemic Sclerosis

The impact of trauma on neutrophil function

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