Interleukin-8–induced suppression of polymorphonuclear leukocyte apoptosis is mediated by suppressing CD95 (Fas/Apo-1) Fas-l interactions

Leuenroth, Stephanie J.; Lee, Christine; Grutkoski, Patricia S.; Keeping, Hugh S.; Simms, Henry S.

doi:10.1016/s0039-6060(98)70148-5

Cited by 68 publications

(53 citation statements)

References 18 publications

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“…This is associated with decreased expression of FasR on neonatal cells, which may account for deficits in the response of these cells to FasL. Our findings are in accordance with reports suggesting that impaired signaling via FasR can contribute to impaired resolution of the inflammatory response in newborns (35). Down-regulation of FasL, as well as caspases, has also been noted during chronic inflammation, which is characterized by persistent neutrophil activity (36).…”

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confidence: 90%

Mechanisms Underlying Reduced Apoptosis in Neonatal Neutrophils

et al. 2005

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Apoptosis, which leads to phagocytosis by mononuclear cells, represents the primary mechanism for removing neutrophils from inflamed tissues and minimizing injury. The present studies show that membrane phosphatidylserine turnover and permeability, as well as DNA fragmentation, were reduced in neutrophils from neonates when compared with adults. The activity of caspase 3 and expression of the proapoptotic proteins Bax, Bad, and Bak were also decreased in neonatal relative to adult neutrophils. These findings are consistent with impaired apoptosis in neonatal cells, which may contribute to prolonged inflammation in infants after oxidative stress or infection. Neutrophil apoptosis is induced by endogenous ligands such as Fas (FasL), which engage death receptors of the tumor necrosis factor/nerve growth factor superfamily, including Fas receptor (FasR). We found that expression of FasR was decreased in neonatal when compared with adult cells. Moreover, neonatal neutrophils did not undergo apoptosis in response to anti-FasR antibody and exhibited impaired chemotaxis to soluble FasL. However, in both adult and neonatal cells, p38 mitogen-activated protein kinase and phosphatidylinositol 3-kinase inhibitors blocked Fas-induced activity. These data suggest that prolonged survival of neonatal neutrophils at injured sites is due, in part, to reduced responsiveness to FasL. This may be related to decreased expression of both FasR and Bcl-2-family proteins that mediate neutrophil apoptosis. Human neutrophils are the primary effector cells in acute inflammation and are rapidly recruited from the bloodstream to injured sites. Although neutrophils from newborns exhibit defects in chemotaxis, phagocytosis, and oxidative metabolism (1-4), infants are at high risk for neutrophil-mediated tissue injury. Activated neutrophils are cleared from inflamed sites by the process of apoptosis, followed by macrophage phagocytosis. This promotes resolution rather than persistence of tissue injury (5,6). Attenuation of neutrophil apoptosis in neonates may contribute to severe and prolonged inflammatory responses. In premature infants, this may play a role in conditions such as bronchopulmonary dysplasia and necrotizing enterocolitis, which result in significant mortality and morbidity.Neutrophil longevity and functional activity are regulated by inflammatory mediators present in the microenvironment.Whereas proinflammatory cytokines, such as interferon-␥ (IFN-␥), granulocyte-monocyte colony-stimulating factor (GM-CSF), and bacterial-derived lipopolysaccharide (LPS), promote neutrophil activation and survival, anti-inflammatory mediators, such as IL-10 (IL-10) and Fas ligand (FasL), are proapoptotic (7-10). These mediators regulate the expression of pro-and antiapoptotic mitochondrial proteins, including Bak, Bad, Bax, and A1, as well as the proapoptotic effector protease caspase 3 (10 -14). Previous studies have demonstrated that the rate of apoptosis is reduced in peripheral blood neutrophils from neonates relative to adult cells (15,16). W...

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confidence: 90%

Mechanisms Underlying Reduced Apoptosis in Neonatal Neutrophils

et al. 2005

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“…IL-8 has also been shown to delay the apoptosis of neutrophils (15,43). Although PMN produced high amounts of IL-8 upon coculture with Leishmania, the IL-8-containing supernatants had no antiapoptotic effect on freshly isolated neutrophils.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of the Spontaneous Apoptosis of Neutrophil Granulocytes by the Intracellular Parasite Leishmania major

Aga

Katschinski

Zandbergen

et al. 2002

The Journal of Immunology

258

240

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Macrophages are the major target cell population of the obligate intracellular parasites Leishmania. Although polymorphonuclear neutrophil granulocytes (PMN) are able to internalize Leishmania promastigotes, these cells have not been considered to date as host cells for the parasites, primarily due to their short life span. In vitro coincubation experiments were conducted to investigate whether Leishmania can modify the spontaneous apoptosis of human PMN. Coincubation of PMN with Leishmania major promastigotes resulted in a significant decrease in the ratio of apoptotic neutrophils as detected by morphological analysis of cell nuclei, TUNEL assay, gel electrophoresis of low m.w. DNA fragments, and annexin V staining. The observed antiapoptotic effect was found to be associated with a significant reduction of caspase-3 activity in PMN. The inhibition of PMN apoptosis depended on viable parasites because killed Leishmania or a lysate of the parasites did not have antiapoptotic effect. L. major did not block, but rather delayed the programmed cell death of neutrophils by ∼24 h. The antiapoptotic effect of the parasites could not be transferred by the supernatants, despite secretion of IL-8 by PMN upon coculture with L. major. In vivo, intact parasites were found intracellularly in PMN collected from the skin of mice 3 days after s.c. infection. This finding strongly suggests that infection with Leishmania prolongs the survival time of neutrophils also in vivo. These data indicate that Leishmania induce an increased survival of neutrophil granulocytes both in vitro and in vivo.

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“…TNF-a probably also causes additional neutrophil recruitment via the stimulation of IL-8 release from bronchial epithelial cells [94,110,111]. In addition, there is evidence that IL-8 prolongs neutrophil survival, by delaying cell death through apoptosis [112,113]. These events may have a functional impact, since there are data compatible with TNF-a and IL-8 causing bronchial hyperresponsiveness in guinea pig and mouse airways in vivo [95,114,115].…”

Section: Neutrophil-accumulating Factorsmentioning

confidence: 99%

Neutrophils, interleukin-17A and lung disease

Lindén¹

2005

Eur Respir J

221

182

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It is now established that an excessive and sustained mobilisation of neutrophils is a hallmark of several chronic inflammatory lung disorders, including severe obstructive lung disease. This article reviews evidence that the cytokine interleukin (IL)-17A is a major orchestrator of sustained neutrophilic mobilisation.Current evidence suggests that IL-17A is produced by T-lymphocytes, and that it exerts an orchestrating effect on the accumulation and associated activity of neutrophils in the bronchoalveolar space indirectly, through an induced release of specific cytokines and colonystimulating factors in resident lung cells.Although the involvement of IL-17A in inflammatory lung disorders is supported by several recent studies, its causative role is still uncertain.However, the unique position of interleukin-17A at the interface between acquired and innate immunity puts this cytokine forward as an important signal for the reinforcement of host defence; it also implies that interleukin-17A may constitute a useful target for pharmacotherapeutic intervention.

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Interleukin-8–induced suppression of polymorphonuclear leukocyte apoptosis is mediated by suppressing CD95 (Fas/Apo-1) Fas-l interactions

Cited by 68 publications

References 18 publications

Mechanisms Underlying Reduced Apoptosis in Neonatal Neutrophils

Mechanisms Underlying Reduced Apoptosis in Neonatal Neutrophils

Inhibition of the Spontaneous Apoptosis of Neutrophil Granulocytes by the Intracellular Parasite Leishmania major

Neutrophils, interleukin-17A and lung disease

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