Expression and regulation of B7 family molecules on macrophages (MΦ) in preterm and term neonatal cord blood and peripheral blood of adults

Orlikowsky, Thorsten; Spring, Bärbel; Dannecker, Günther; Niethammer, D.; Poets, Christian F.; Hoffmann, Michael K.

doi:10.1002/cyto.b.10033

Cited by 31 publications

(42 citation statements)

References 47 publications

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“…Comparing the expression pattern of Bcl-2 and Bcl-xL in monocytes and lymphocytes, Okada et al (20) found that Bcl-xL was predominantly expressed in differentiating cells. Our data show a higher expression of Bcl-xL in CBMO as compared with PBMO, which might point to a different state of differentiation of these cells, underlining former results concerning their immaturity in phenotype and function (24). Upregulation of Bcl-xL may therefore be an important process in preventing CBMO from PICD as functionally seen.…”

Section: Discussionsupporting

confidence: 66%

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: Discussionsupporting

confidence: 66%

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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“…As shown earlier (20,22), αCD3 mAb-mediated T-cell proliferation in uninfected CBMCs was diminished as compared with that of PBMCs (28% (15-80%) vs. 64% (40-85%), Figure 5b). Infection of monocytes resulted in a greatly diminished αCD3-mediated T-cell proliferation in PBMCs as compared with their uninfected counterparts (21% (12-82%), Figure 5b), whereas T-cell proliferation in CBMCs was increased (82% (46-89%), Figure 5b).…”

Section: Remaining Cbmos Are Capable Of Inducing T-cell Proliferationsupporting

confidence: 73%

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

et al. 2012

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Background:The propensity for sustained inflammation after bacterial infection in neonates, resulting in inflammatory sequelae such as bronchopulmonary dysplasia and periventricular leucomalacia, is well known, but its molecular mechanisms remain elusive. Termination of inflammatory reactions physiologically occurs early after removal of bacteria by phagocytosis-induced cell death (PIcD) of immune effector cells such as monocytes. PIcD from cord blood monocytes (cBMOs) was shown to be reduced as compared with that of peripheral blood monocytes (PBMOs) from adult donors in vitro. Methods: PBMOs, cBMOs, and Fas (cD95)-deficient (lpr) mouse monocytes were analyzed in an in vitro infection model using green fluorescence protein-labeled Escherichia coli (E. coli-GFP). Phagocytosis and apoptosis were quantified by flow cytometry and cD95L secretion was quantified by enzyme-linked immunosorbent assay. results: We demonstrate the involvement of the cD95/ cD95 ligand pathway (cD95/cD95L) in PIcD and provide evidence that diminished cD95L secretion by cBMOs may result in prolonged activation of neonatal immune effector cells. conclusion: These in vitro results offer for the first time a molecular mechanism accounting for sustained inflammation seen in neonates.

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“…Consistent with this observation, M⌽-dependent T cell activation is reduced in neonates, and CBM⌽ preferentially deliver negative signals to T cells (16).…”

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confidence: 70%

“…Cord blood macrophages (CBM⌽) per se exhibit a reduced co-stimulatory potential: CD80 and CD86 expression and upregulation are significantly inhibited in CBM⌽ compared with M⌽ from adult donors (16). Consistent with this observation, M⌽-dependent T cell activation is reduced in neonates, and CBM⌽ preferentially deliver negative signals to T cells (16).…”

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Effect of Dexamethasone on B7 Regulation and T Cell Activation in Neonates and Adults

et al. 2005

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The safety of dexamethasone for neonates has been questioned, partly because of its multiple unspecific effects on the immune system. Specific effects of dexamethasone on costimulatory and immune suppressive functions of neonatal compared with adult macrophages (M⌽) are not known. We evaluated the effect of dexamethasone on the expression and regulation of M⌽ B7 family receptors (B7-1, CD80; B7-2, CD86) and on their ability to co-stimulate T cells. Cord blood macrophages (CBM⌽) and M⌽ from healthy adults (PBM⌽) were isolated, and cell surface markers were phenotyped by flow cytometry. In tissue culture, cells were exposed to dexamethasone, interferon-␥ (IFN-␥), cAMP, or a T cell mitogen (␣CD3) and examined for their capacity to activate or destroy T cells. CBM⌽ were less able to up-regulate CD80 and CD86 than PBM⌽ (p Ͻ 0.05). Dexamethasone inhibited the up-regulation of CD80, CD86, and HLA-DR on PBM⌽ and even more so on CBM⌽ (p Ͻ 0.05 versus PBM⌽ for CD80 and CD86). In the presence of dexamethasone, stimulation with ␣CD3 MAb enhanced cytotoxic functions of PMBM⌽ and CB⌴⌽ with an increase in deleted T cells, a reduced fraction of enlarged T cells, and an inhibition of T cell CD28 up-regulation, which again were more pronounced with CBM⌽ (p Ͻ 0.05 versus PBM⌽). In conclusion, neonatal M⌽ are exquisitely sensitive to the inhibitory effects of dexamethasone on B7 expression. Although perhaps producing the desired therapeutic effect, dexamethasone may do so in newborns at the expense of a near complete paralysis of M⌽-dependent T cell function. Preterm newborns have been exposed to dexamethasone for the prevention or treatment of bronchopulmonary dysplasia (BPD) for many years (1,2). Dexamethasone is a synthetic glucocorticoid that reduces the recruitment of inflammatory cells (3,4) and thereby is thought to inhibit the development of BPD. Its effects on other developing organs such as the CNS were only recognized much later. Because follow up-studies provided evidence of abnormal neurodevelopment, early postnatal use of dexamethasone is not recommended any more (2). Nevertheless, glucocorticoids continue to be given to pregnant women to accelerate fetal lung development.Besides the endocrinium, the primary target of dexamethasone is the immune system, which is incompletely developed in neonates. Evidence that the immunosuppressive effects of dexamethasone are primarily mediated via an inhibition of cytokine production has been produced. Mononuclear cells from adults and neonates respond differently to treatment with dexamethasone. With respect to proinflammatory cytokines, cord blood cells show an increased sensitivity toward the inhibitory action of dexamethasone compared with cells from adult donors, resulting in a more pronounced inhibition of IL-1␤, IL-6, tumor necrosis factor-␣, 6).Dexamethasone may directly inhibit T cell proliferation (7), induce apoptosis (8), promote long-lasting changes in the T cell receptor v␤ repertoire (9), or decrease the CD4/CD8 ratio in infants with BPD (10). Dexamethasone also infl...

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Expression and regulation of B7 family molecules on macrophages (MΦ) in preterm and term neonatal cord blood and peripheral blood of adults

Cited by 31 publications

References 47 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

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

Effect of Dexamethasone on B7 Regulation and T Cell Activation in Neonates and Adults

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