Phagocytosis by neutrophils

Lee, Warren L.; Harrison, Rene E.; Grinstein, Sergio

doi:10.1016/j.micinf.2003.09.014

Cited by 328 publications

(267 citation statements)

References 43 publications

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“…The killing of bacteria such as E. coli by neutrophils is a complex process that involves multiple sequential steps including the expression of specific surface receptors, secretion of granule contents, binding of bacteria to neutrophil surface receptors, internalization (phagocytosis), and intracellular killing (33). Neutrophil extracellular traps may also degrade virulence factors and kill extracellular bacteria (34).…”

Section: Cpla 2 -α-Mediated Arachidonic Acid Release Is Necessary Formentioning

confidence: 99%

“…Subsequent maturation of developing phagosomes proceeds by complex processes that include recruitment and activation of the NADPH oxidase, fusion of phagosomes with intracellular lysosomal granules, and acidification of the phagolysosome (33). A potential role for cPLA 2 -α in neutrophil-bacterial killing is suggested by the translocation of cPLA 2 -α from the cytosol to phagosomes during the early stages of phagocytosis (5).…”

Section: Role Of Cpla 2 In Neutrophil-mediated Bacterial Killing and mentioning

confidence: 99%

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Cytosolic Phospholipase A2-α Is Necessary for Platelet-activating Factor Biosynthesis, Efficient Neutrophil-mediated Bacterial Killing, and the Innate Immune Response to Pulmonary Infection

Rubin

Downey

Koh

et al. 2005

Journal of Biological Chemistry

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The role of a cytosolic phospholipase A 2 -α (cPLA 2 -α) in neutrophil arachidonic acid release, plateletactivating factor (PAF) biosynthesis, NADPH oxidase activation, and bacterial killing in vitro, and the innate immune response to bacterial infection in vivo was examined. cPLA 2 -α activity was blocked with the specific cPLA 2 -α inhibitor, Pyrrolidine-1 (human cells), or by cPLA 2 -α gene disruption (mice). cPLA 2 -α inhibition or gene disruption led to complete suppression of neutrophil arachidonate release and PAF biosynthesis but had no effect on neutrophil NADPH oxidase activation, FcγII/III or CD11b surface expression, primary or secondary granule secretion, or phagocytosis of Escherichia coli in vitro. In contrast, cPLA 2 -α inhibition or gene disruption diminished neutrophil-mediated E. coli killing in vitro, which was partially rescued by exogenous arachidonic acid or PAF but not leukotriene B 4 . Following intratracheal inoculation with live E. coli in vivo, pulmonary PAF biosynthesis, inflammatory cell infiltration, and clearance of E. coli were attenuated in cPLA 2 -α (−/−) mice compared with wild type littermates. These studies identify a novel * This work was supported by grants from The Physicians of Ontario through The P.S.I. Foundation (Grant 01-12 (to B. B. R.) and 98-049

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Section: Cpla 2 -α-Mediated Arachidonic Acid Release Is Necessary Formentioning

confidence: 99%

Section: Role Of Cpla 2 In Neutrophil-mediated Bacterial Killing and mentioning

confidence: 99%

Cytosolic Phospholipase A2-α Is Necessary for Platelet-activating Factor Biosynthesis, Efficient Neutrophil-mediated Bacterial Killing, and the Innate Immune Response to Pulmonary Infection

Rubin

Downey

Koh

et al. 2005

Journal of Biological Chemistry

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“…The analysis of the determinants of phagosomal pH is a complex matter because several proton transporters such as V-ATPase, NHE-1 and Hv1 (which was not identified until 2006) can regulate the phagosomal pH at different times during the phagocytic process. The phagosomes of neutrophils eventually acidify, and as in macrophages the phagosomal acidification is required for the optimal activity of proteases and lysosomal hydrolases involved in pathogen killing and for phagosome maturation (Lee et al, 2003). The delayed acidification of neutrophil phagosomes is linked to the activity of the NADPH oxidase on the phagosomal membrane, which is greater in neutrophils than in macrophages.…”

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confidence: 99%

Do Hv1 proton channels regulate the ionic and redox homeostasis of phagosomes?

Chemaly

Demaurex

2012

Molecular and Cellular Endocrinology

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a b s t r a c tRecent work on animal models has revealed the important role played by the voltage-gated proton channel Hv1 during bacterial killing by innate immune cells. Studies from mice lacking Hv1 channels showed that Hv1 proton channels are required for high-level production of reactive oxygen species (ROS) by the NADPH oxidase of phagocytes (NOX2) in two ways. First, Hv1 channels maintain a physiological membrane potential during the respiratory burst of neutrophils by providing a compensating charge for the electrons transferred by NOX2 from NADPH to superoxide. Second, Hv1 channels maintain a physiological cytosolic pH by extruding the acid generated by the NOX2-dependent consumption of NADPH. The two mechanisms directly sustain the activity of the NOX2 enzyme and indirectly sustain other neutrophil functions by enhancing the driving force for the entry of calcium into cells, thereby boosting cellular calcium signals. The increased depolarization of Hv1-deficient neutrophils aborted calcium responses to chemoattractants and revealed adhesion and migration defects that were associated with an impaired depolymerization of the cortical actin cytoskeleton. Current research aims to transpose these findings to phagosomes, the phagocytic vacuoles where bacterial killing takes place. However, the mechanisms that control the phagosomal pH appear to vary greatly between phagocytes: phagosomes rapidly acidify in macrophages but remain neutral for several minutes in neutrophils following ingestion of solid particles, whereas in dendritic cells phagosomes alkalinize, a mechanism thought to promote antigen crosspresentation. In this review, we discuss how the knowledge gained on the role of Hv1 channels at the plasma membrane of neutrophils can be used to study the regulation of the phagosomal pH, ROS, membrane potential, and calcium fluxes in different phagocytic cells.

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“…Dependendo do tipo de interação entre os PMNs e os micro-organismos, a ingestão do patógeno pode ocorrer tanto com a emissão de pseudópodes, rodeando e internalizando a partícula (ativação de receptores Fc), como através do "afundamento" das partículas para dentro da célula (ativação dos receptores de complemento) (Lee et al, 2003;Amulic et al, 2012).…”

Section: -Fagocitoseunclassified

“…A destruição dos patógenos ocorre tanto através de mecanismos independentes de oxigênio (com a ação das substâncias tóxicas contidas nos grânulos) como através de mecanismos dependentes de oxigênio (com a produção de ERO com grande potencial microbicida) (Lee et al, 2003;Mayer-Scholl et al, 2004;Amulic et al, 2012;Kolaczkowska;Kubes, 2013).…”

Section: -Fagocitoseunclassified

O extrato etanólico das folhas de Baccharis dracunculifolia (Asteraceae) modula funções efetoras de neutrófilos: um promissor agente fitoterápico para o tratamento de processos inflamatórios mediados por estas células

Rinhel¹

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RibeirãoNeutrophils are phagocytic immune cells mobilized primarily to fight against infections. These cells are capable to kill microorganisms through degranulation, which leads to the release of antimicrobial molecules, and production of reactive oxygen species. Although neutrophil recruitment is essential for host protection, excessive activation of these cells culminates in intense discharge of cytotoxic molecules to the extracellular milieu, which can elicit the development of and/or aggravate the clinical condition in autoimmune and inflammatory diseases such as rheumatoid arthritis. Modulation of the effector functions of neutrophils is a possible therapeutic approach to treat these diseases. Previous studies have shown that the ethanolic extract of Baccharis dracunculifolia leaves (EEBd) has a great therapeutic potential due to its significant antioxidant effect towards the oxidative metabolism of neutrophils. To continue investigating the anti-inflammatory and/or immunomodulatory action of such extract, the first part of the present work examined its modulator effect on three important effector functions of human neutrophils that mediate recognition and clearance of pathogens -phagocytosis, degranulation, and microbial killing -and on the activity of lysosomal enzymes. EEBd inhibited the oxidative metabolism of neutrophils without affecting their defense ability, depending on the extract concentration used. To propose possible chemical markers for the biological effects of the extract, the second part of this study evaluated the antioxidant activity of seven compounds isolated from EEBd -caffeic acid, coumaric acid, ferulic acid, cinnamic acid, aromadendrin-4'-methyl ether, isosakuranetin, and hispidulin -towards the oxidative metabolism of neutrophils. The results pointed to caffeic acid as a potential chemical marker for this biological activity. The third part of this investigation aimed to improve the bioavailability and favor the therapeutic use of the natural products studied. EEBd and caffeic acid were incorporated into liposomal carrier systems. The incorporation of both samples into liposomes did not alter their antioxidant activity towards neutrophils, as compared with their respective free forms. Finally, this study examined the therapeutic effect of EEBd and caffeic acid, both in the free form and incorporated into liposomes, in an animal model of arthritis. The free samples markedly improved the joint inflammatory parameters: they reduced edema and migration of total cells and neutrophils, and slightly lowered the levels of the inflammatory cytokines tumor necrosis factor  and interleukin 6 and 1 (TNF-, IL-6, and IL-1, respectively). In addition, incorporation of EEBd and caffeic acid into liposomes can help to reduce their concentrations required to achieve the desired therapeutic effect. Based on the set of results obtained in this study, we conclude that EEBd has a great potential to become a therapeutic adjuvant in the treatment of neutrophil-mediated inflammatory diseases, and that...

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Phagocytosis by neutrophils

Cited by 328 publications

References 43 publications

Cytosolic Phospholipase A2-α Is Necessary for Platelet-activating Factor Biosynthesis, Efficient Neutrophil-mediated Bacterial Killing, and the Innate Immune Response to Pulmonary Infection

Cytosolic Phospholipase A2-α Is Necessary for Platelet-activating Factor Biosynthesis, Efficient Neutrophil-mediated Bacterial Killing, and the Innate Immune Response to Pulmonary Infection

Do Hv1 proton channels regulate the ionic and redox homeostasis of phagosomes?

O extrato etanólico das folhas de Baccharis dracunculifolia (Asteraceae) modula funções efetoras de neutrófilos: um promissor agente fitoterápico para o tratamento de processos inflamatórios mediados por estas células

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