Polymorphonuclear Leukocyte Function

Boxer, Grace Jordison; Curnutte, John T.; Boxer, Laurence A.

doi:10.1080/21548331.1985.11703014

Cited by 49 publications

(22 citation statements)

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“…Potential N-linked glycosylation sites in the bovine amino acid sequence with the consensus sequence N-X-(S/T) are indicated by arrowheads. Other functional regions mapped to the human gp91-phox protein are underlined and include putative p47-phox binding sites (labeled [1][2][3][4] [33,35,57], potential flavin binding domains (labeled A and B) [29,44], and potential NADPH binding domains (labeled C-F) [28,29]. See text for further details.…”

Section: Discussionmentioning

confidence: 99%

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Cloning and sequencing of the bovine flavocytochrome b subunit proteins, gp91-phox and p22-phox: comparison with other known flavocytochrome b sequences

Davis

Mascolo

Bunger

et al. 1998

Journal of Leukocyte Biology

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Section: Discussionmentioning

confidence: 99%

“…Neutrophils represent one of the first lines of defense against invading organisms in the body and are key mediators in the inflammatory response [1]. On exposure to a pathogen, the neutrophil responds by generating toxic oxygen metabolites [2,3].…”

Section: Introductionmentioning

confidence: 99%

Cloning and sequencing of the bovine flavocytochrome b subunit proteins, gp91-phox and p22-phox: comparison with other known flavocytochrome b sequences

Davis

Mascolo

Bunger

et al. 1998

Journal of Leukocyte Biology

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“…Polymorphonuclear leukocytes (PMNs) 1 participate in host defense by releasing antimicrobial proteins from intracellular granules into phagosomes. A number of highly specialized functions, including chemotaxis, adhesion, superoxide production, and secretion of hydrolytic enzymes, permit PMNs to accomplish this complex task (1,2).…”

mentioning

confidence: 99%

“…A number of highly specialized functions, including chemotaxis, adhesion, superoxide production, and secretion of hydrolytic enzymes, permit PMNs to accomplish this complex task (1,2). The signaling pathways involved in phagocytosis are determined by the activation state of the PMN, as well as by the type of agonist used for activation.…”

mentioning

confidence: 99%

The Formation of Ceramide-1-phosphate during Neutrophil Phagocytosis and Its Role in Liposome Fusion

Hinkovska‐Galcheva¹,

Boxer²,

Mansfield³

et al. 1998

Journal of Biological Chemistry

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123

108

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Ceramide, a product of agonist-stimulated sphingomyelinase activation, is known to be generated during the phagocytosis of antibody-coated erythrocytes by polymorphonuclear leukocytes. Agonist-stimulated formation of ceramide-1-phosphate is now shown to occur in 32 PO 4 -labeled neutrophils. Ceramide-1-phosphate is formed by a calcium-dependent ceramide kinase, found predominately in the neutrophil plasma membrane. The neutrophil kinase is specific for ceramide because, in contrast to the bacterial diglyceride kinase, ceramide is not phosphorylated under conditions specific for diglyceride phosphorylation. Conversely, 1,2-diacylglycerol does not serve as substrate for the neutrophil ceramide kinase. Ceramide kinase activation occurs in a time-dependent fashion, reaching peak activity 10 min after formyl peptide stimulation and challenge with antibody-coated erythrocytes. The lipid kinase activity is optimal at pH 6.8. Because the formation of the phagolysosome is a critical event in phagocytosis, the effect of ceramide-1-phosphate in promoting the fusion of liposomes was determined. Both the addition of increasing concentrations of sphingomyelinase D and ceramide-1-phosphate promoted liposomal fusion. In summary, ceramide-1-phosphate is formed during phagocytosis through activation of ceramide kinase. Ceramide-1-phosphate may promote phagolysosome formation.

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“…1 and 2). During the inflammatory response, neutrophils are readily mobilized to sites of inflammation, where they phagocytose pathogens and/or fragments of damaged tissue and subsequently release a variety of toxic oxygen radical species which can destroy the engulfed material (1,2). The generation of oxygen radicals by neutrophils is known as the respiratory burst and results from the activation of a membrane-bound NADPH oxidase (reviewed in Refs.…”

mentioning

confidence: 99%

Analysis of Activation-induced Conformational Changes in p47 Using Tryptophan Fluorescence Spectroscopy

Swain

Helgerson

Davis

et al. 1997

Journal of Biological Chemistry

100

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Activation of the neutrophil NADPH oxidase requires translocation of cytosolic proteins p47phox , p67 phox , and Rac to the plasma membrane or phagosomal membrane, where they assemble with membrane-bound flavocytochrome b. During this process, it appears that p47 phox undergoes conformational changes, resulting in the exposure of binding sites involved in assembly and activation of the oxidase. In the present study, we have directly evaluated activation-induced conformational changes in p47 phox using tryptophan fluorescence and circular dichroism spectroscopy. Treatment of p47 phox with amphiphilic agents known to activate the NADPH oxidase (SDS and arachidonic acid) caused a dose-dependent quenching in the intrinsic tryptophan fluorescence of p47 phox , whereas treatment with a number of other amphiphilic agents that failed to activate the oxidase had no effect on p47 phox fluorescence. In addition, the concentration range of activating agents required to induce changes in fluorescence correlated with the concentration range of these agents that induced maximal NADPH oxidase activity in a cell-free assay system. We next determined if activation by phosphorylation caused the same type of conformational changes in p47 phox . Protein kinase C phosphorylation of p47 phox in vitro resulted in comparable quenching of fluorescence, which also correlated directly with NADPH oxidase activity. Finally, the circular dichroism (CD) spectrum of p47 phox was significantly changed by the addition of SDS, whereas treatment with a non-activating detergent had no effect on the CD spectrum. These results support the conclusion that activation by amphiphilic agents results in changes in the secondary structure of p47 phox . Thus, our studies provide direct evidence linking conformational changes in p47 phox to the NADPH oxidase activation/assembly process and also further support the hypothesis that amphiphile-mediated activation of the NADPH oxidase induces changes in p47 phox that are similar to those mediated by phosphorylation in vivo.

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Polymorphonuclear Leukocyte Function

Cited by 49 publications

References 0 publications

Cloning and sequencing of the bovine flavocytochrome b subunit proteins, gp91-phox and p22-phox: comparison with other known flavocytochrome b sequences

Cloning and sequencing of the bovine flavocytochrome b subunit proteins, gp91-phox and p22-phox: comparison with other known flavocytochrome b sequences

The Formation of Ceramide-1-phosphate during Neutrophil Phagocytosis and Its Role in Liposome Fusion

Analysis of Activation-induced Conformational Changes in p47 Using Tryptophan Fluorescence Spectroscopy

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