The CD95/CD95L pathway is involved in phagocytosis-induced cell death of monocytes and may account for sustained inflammation in neonates

Gille, Christian; Dreschers, Stephan; Leiber, Anja; Lepiorz, Florian; Krusch, Matthias; Grosse-Opphoff, Julia; Spring, Baerbel; Haas, Martin; Urschitz, Michael S.; Poets, Christian F.; Orlikowsky, Thorsten

doi:10.1038/pr.2012.196

Cited by 20 publications

(26 citation statements)

References 37 publications

(51 reference statements)

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“…Yet, only alterations in the activation of the extrinsic apoptosis pathway of CBMO have been described, i.e., a diminished release and impact of the two death ligands CD95L (13) and TNF-α (36). We now show that the regulation of Bcl-2 family proteins and the following steps in the intrinsic apoptosis signaling pathway also differ between CBMO and PBMO.…”

Section: Articlesmentioning

confidence: 82%

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Neonatal monocytes express antiapoptotic pattern of Bcl-2 proteins and show diminished apoptosis upon infection with Escherichia coli

et al. 2014

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Background:Neonates show sustained inflammation after a bacterial infection, which is associated with inflammatory diseases like bronchopulmonary dysplasia or periventricular leucomalacia. Physiologically, inflammation is terminated early after the removal of the invading pathogens by phagocytosisinduced cell death (PICD) of immune effector cells. Earlier results showed reduced PICD in neonatal monocytes. The underlying molecular mechanisms are unknown. We hypothesize that the reduced PICD in neonatal monocytes is regulated through the proteins of the B-cell lymphoma 2 (Bcl-2) protein family. Methods: mRNA and protein expression of Bcl-2 family proteins in cord blood and adult peripheral blood monocytes infected with Escherichia coli were analyzed by quantitative real-time PCR and flow cytometry and cytochrome c release by fluorescence microscopy. results: mRNA expression of antiapopototic Bcl-xL was upregulated in cord blood monocytes (CBMO), whereas proapoptotic Bim tended to be higher in peripheral blood monocytes (PBMO). Upon infection, Bax was more strongly expressed in PBMO compared with CBMO. The pro/antiapoptotic balance was skewed toward survival in CBMO and apoptosis in PBMO. Cytochome c release into the cytosol was enhanced in PBMO compared with CBMO. conclusion: Bcl-2 proteins are involved in reduced PICD in neonatal monocytes. These findings are another step toward the understanding of sustained inflammation in neonates.

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Section: Articlesmentioning

confidence: 82%

“…The CD95L pathway of apoptosis was shown to be crucial for monocyte apoptosis after bacterial infection. However, CD95L secretion was strongly reduced in CBMO, while external CD95L could restore CBMO apoptosis (8,13).…”

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confidence: 99%

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Neonatal monocytes express antiapoptotic pattern of Bcl-2 proteins and show diminished apoptosis upon infection with Escherichia coli

et al. 2014

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“…[6] These include persistence of an inflammatory stimulus,[48] hampered resolution of inflammation,[49, 50] a pro-inflammatory profile characteristic of extremely preterm newborns,[51, 52] limited ability to degrade inflammation-related proteins,[53-55] positive feedback loops between innate and adaptive immune systems,[56] epigenetic phenomena,[57] endoplasmic reticulum stress resulting in an unfolded protein response,[58] impairments of ubiquitylation,[59] and impairments of autophagy. [60]…”

Section: Discussionmentioning

confidence: 99%

Systemic inflammation on postnatal days 21 and 28 and indicators of brain dysfunction 2years later among children born before the 28th week of gestation

Leviton

Allred

Fichorova

et al. 2016

Early Human Development

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Background Systemic inflammation during the first two postnatal weeks in extremely preterm newborns (< 28 weeks gestation) has been associated with an increased risk of neurodevelopmental dysfunctions. Little is known, however, about the relationship between systemic inflammation during the third and fourth postnatal weeks and subsequent development. Methods We measured the concentrations of 16 inflammation-related proteins in blood spots collected on postnatal days 21 (N = 749) and 28 (N = 697) from infants born before the 28th week of gestation and assessed at age 2 years. We then sought the developmental correlates of top quartile concentrations for gestational age and day the specimen was collected. Odds ratios and 95% confidence intervals were calculated from regular or multinomial logistic regression models (as appropriate). Results Top quartile concentrations of CRP, IL-1β, IL-6, IL-6R, TNF-R2, IL-8, ICAM-1, and TSH on both days 21 and 28 were associated with ventriculomegaly (when in the NICU) and microcephaly at age 2 years. Top quartile concentrations of CRP, SAA, IL-6, TNF-R2, IL-8, and ICAM-1 were associated with Mental Development Index (MDI) of the Bayley-II < 55, while top quartile concentrations of CRP, TNF-α (inversely), IL-8, and ICAM-1 were associated with Psychomotor Development Index (PDI) < 55 Conclusion Extremely preterm newborns who had systemic inflammation during the third and fourth postnatal weeks were at increased risk of ventriculomegaly during the months after birth, and of microcephaly, and low Bayley Scale scores at 2 years of age.

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“…Under physiological conditions, apoptosis of activated monocytes and neutrophils [1] and polarization of macrophages from a proinflammatory M1 phenotype towards an anti-inflammatory M2 phenotype prevent the hyper-responsiveness of the innate immunity [22]. Cord blood-derived monocytes and neutrophils appear to be more resistant to apoptosis than adult peripheral blood-derived cells [23,24]. The surviving neutrophils contribute to sustained inflammation through the secretion of particularly high levels of pro-inflammatory cytokines after LPS stimulation in vitro [23].…”

Section: The Neonatal Immune System Is Immature and Incapable Of Manamentioning

confidence: 99%

MSCS in Scenarios of Infection and Inflammation: Focus on Neonatal Diseases

Pierro

Thébaud

2016

Curr Stem Cell Rep

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The imbalance of inflammatory and antiinflammatory responses in favor of inflammation plays a major role in the pathogenesis of many neonatal diseases. Inflammation in the perinatal period carries important longterm consequences, including neurodevelopmental and respiratory complications. Treatments able to restore immune homeostasis may reduce neonatal mortality and prevent longterm deleterious multi-organ consequences of unchecked inflammation. Mesenchymal stromal cells are a heterogenous group of progenitors cells with potent anti-inflammatory and immunomodulatory potential, among other diverse mechanisms of action. Thus, mesenchymal stromal cells (MSCs) may represent a novel and effective therapy for several neonatal diseases, potentially capable of preventing their longterm complications. This paper reviews the role of inflammation in the perinatal period and the therapeutic role of MSCs, focusing on their anti-inflammatory potential.

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The CD95/CD95L pathway is involved in phagocytosis-induced cell death of monocytes and may account for sustained inflammation in neonates

Cited by 20 publications

References 37 publications

Neonatal monocytes express antiapoptotic pattern of Bcl-2 proteins and show diminished apoptosis upon infection with Escherichia coli

Neonatal monocytes express antiapoptotic pattern of Bcl-2 proteins and show diminished apoptosis upon infection with Escherichia coli

Systemic inflammation on postnatal days 21 and 28 and indicators of brain dysfunction 2years later among children born before the 28th week of gestation

MSCS in Scenarios of Infection and Inflammation: Focus on Neonatal Diseases

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