Serum stromal-derived-factor-1 (CXCL12) and its alpha chemokine receptor (CXCR4) as biomarkers in neonatal sepsis

Badr, Hassan; El-Gendy, Fady M; Helwa, Mohamed A

doi:10.1080/14767058.2017.1336760

Cited by 14 publications

(19 citation statements)

References 23 publications

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“…In a model of polymicrobial sepsis, blocking CXCR4 decreased sepsis-induced mortality (55). Additionally, Gosh et al demonstrated that inhibition of CXCR4 reduced migration of cells by regulating cytoskeletal remodeling (56) and CXCR4 is considered as biomarker for peritoneal sepsis (57). Nevertheless, data on CXCR4 and sepsis is still conflicting.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of CXCR4 and CXCR7 Is Protective in Acute Peritoneal Inflammation

et al. 2020

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Our previous studies revealed a pivotal role of the chemokine stromal cell-derived factor (SDF)-1 and its receptors CXCR4 and CXCR7 on migratory behavior of polymorphonuclear granulocytes (PMNs) in pulmonary inflammation. Thereby, the SDF-1-CXCR4/CXCR7-axis was linked with adenosine signaling. However, the role of the SDF-1 receptors CXCR4 and CXCR7 in acute inflammatory peritonitis and peritonitis-related sepsis still remained unknown. The presented study provides new insight on the mechanism of a selective inhibition of CXCR4 (AMD3100) and CXCR7 (CCX771) in two models of peritonitis and peritonitis-related sepsis by injection of zymosan and fecal solution. We observed an increased expression of SDF-1, CXCR4, and CXCR7 in peritoneal tissue and various organs during acute inflammatory peritonitis. Selective inhibition of CXCR4 and CXCR7 reduced PMN accumulation in the peritoneal fluid and infiltration of neutrophils in lung and liver tissue in both models. Both inhibitors had no anti-inflammatory effects in A 2B knockout animals (A 2B-/-). AMD3100 and CCX771 treatment reduced capillary leakage and increased formation of tight junctions as a marker for microvascular permeability in wild type animals. In contrast, both inhibitors failed to improve capillary leakage in A 2B-/-animals, highlighting the impact of the A 2B-receptor in SDF-1 mediated signaling. After inflammation, the CXCR4 and CXCR7 antagonist induced an enhanced expression of the protective A 2B adenosine receptor and an increased activation of cAMP (cyclic adenosine mono phosphate) response element-binding protein (CREB), as downstream signaling pathway of A 2B. The CXCR4-and CXCR7-inhibitor reduced the release of cytokines in wild type animals via decreased intracellular phosphorylation of ERK and NFκB p65. In vitro, CXCR4 and CXCR7 antagonism diminished the chemokine release of human cells and increased cellular integrity by enhancing the expression of tight junctions. These protective effects were linked with functional A 2B-receptor signaling, confirming our in vivo data. In conclusion, our study revealed new protective aspects of the pharmacological modulation of the SDF-1-CXCR4/CXCR7-axis during acute peritoneal inflammation in terms of the two hallmarks PMN migration and barrier integrity. Both anti-inflammatory effects were linked with functional adenosine A 2B-receptor signaling.

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Section: Discussionmentioning

confidence: 99%

Inhibition of CXCR4 and CXCR7 Is Protective in Acute Peritoneal Inflammation

et al. 2020

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“…The expression of CXCR-4 was already shown to be increased on lymphocytes in sepsis [ 22 ] resulting in improved migration and activation. Levels of its ligand SDF-1α are also increased in septic states [ 23 ]. The SDF-1α /CXCR-4 axis is furthermore involved in EPC recruitment to the spleen [ 24 ] and CXCR-4 influences EPC homing through cellular polarization [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

CXCR-4 expression by circulating endothelial progenitor cells and SDF-1 serum levels are elevated in septic patients

et al. 2018

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BackgroundEndothelial progenitor cell (EPC) numbers are increased in septic patients and correlate with survival. In this study, we investigated, whether surface expression of chemokine receptors and other receptors important for EPC homing is upregulated by EPC from septic patients and if this is associated with clinical outcome.MethodsPeripheral blood mononuclear cells from septic patients (n = 30), ICU control patients (n = 11) and healthy volunteers (n = 15) were isolated by Ficoll density gradient centrifugation. FACS-analysis was used to measure the expression of the CXC motif chemokine receptors (CXCR)-2 and − 4, the receptor for advanced glycation endproducts (RAGE) and the stem cell factor receptor c-Kit. Disease severity was assessed via the Simplified Acute Physiology Score (SAPS) II. The serum concentrations of vascular endothelial growth factor (VEGF), stromal cell-derived factor (SDF)-1α and angiopoietin (Ang)-2 were determined with Enzyme linked Immunosorbent Assays.ResultsEPC from septic patients expressed significantly more CXCR-4, c-Kit and RAGE compared to controls and were associated with survival-probability. Significantly higher serum concentrations of VEGF, SDF-1α and Ang-2 were found in septic patients. SDF-1α showed a significant association with survival.ConclusionsOur data suggest that SDF-1α and CXCR-4 signaling could play a crucial role in EPC homing in the course of sepsis.Electronic supplementary materialThe online version of this article (10.1186/s12950-018-0186-7) contains supplementary material, which is available to authorized users.

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“…The levels of serum CXCR4 and CXCL12 in neonatal sepsis were signi cantly higher than those in controls [11,12]. The level of CXCL10 was increased in the blood and peritoneum in a murine model of neonatal polymicrobial sepsis [13].…”

Section: Read Full License Introductionmentioning

confidence: 89%

“…The level of CXCL10 was increased in the blood and peritoneum in a murine model of neonatal polymicrobial sepsis [13]. Furthermore, these cytokines could be used as valuable biomarkers for the diagnosis of neonatal sepsis [8][9][10][11][12]. However, studies on the relationship between cytokine/chemokine levels and severity, and the difference of cytokines/chemokines between early-onset sepsis (EOS) and late-onset sepsis (LOS) are limited.…”

Section: Read Full License Introductionmentioning

confidence: 99%

Expression of Serum Cytokines Profile in Neonatal Sepsis

Kuang

Chen

Huang

et al. 2020

Preprint

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Sepsis remained a major cause of neonatal death, but the pathologic mechanisms were poorly understood. The objective of this study was to characterize the serum cytokine/chemokine profile in neonates with sepsis. In this study, we enrolled 40 full-term neonates with sepsis and 19 neonates without infection as controls. Serum 40 cytokines/chemokines were analyzed using Luminex Bead Immunoassay System. Serum IL-17 was measured using enzyme-linked immune-absorbent assay. Our results showed that serum IL-6, IL-8, TNF-α, IL-1β, MIF, CXCL13, CXCL1, CXCL2, CXCL5, CXCL6, CXCL16, CCL27, CCL2, CCL8, CCL3, CCL20, CCL23, CCL27 and CX3CL1 were significantly increased in neonates with sepsis compared to controls (all p<0.05). The levels of serum CXCL6, CXCL1, IL-6, CXCL10, CXCL11, CCL20, and IL-17 were higher in LOS than those in EOS (all p<0.05). Conversely, serum IL-16, CXCL16, CCL22 were lower in LOS than those in EOS (all p<0.05). The levels of CX3CL1, CXCL2, CCL8 and TNF-α were all positively correlated with SOFA scores. We suggest that excessive pro-inflammatory cytokines might involve in the damage of neonatal sepsis. In addition, chemokines significantly increased the recruitment of immune cells after infection to participate in the anti-infection defense of neonates, but they might lead to damage.

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Serum stromal-derived-factor-1 (CXCL12) and its alpha chemokine receptor (CXCR4) as biomarkers in neonatal sepsis

Abstract: Serum CXCR4 and CXCL12 levels increase significantly in septic neonates and they are valuable marker in diagnosis of neonatal sepsis. Serum concentrations of both chemokines represent promising novel biomarkers for neonatal sepsis.

Cited by 14 publications

References 23 publications

Inhibition of CXCR4 and CXCR7 Is Protective in Acute Peritoneal Inflammation

Inhibition of CXCR4 and CXCR7 Is Protective in Acute Peritoneal Inflammation

CXCR-4 expression by circulating endothelial progenitor cells and SDF-1 serum levels are elevated in septic patients

Expression of Serum Cytokines Profile in Neonatal Sepsis

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