Characterization of peptide diffusion into electropermeabilized neutrophils

DeLeo, Frank R.; Jutila, Mark A.; Quinn, Mark T.

doi:10.1016/0022-1759(96)00144-5

Cited by 24 publications

(15 citation statements)

References 64 publications

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“…This region was previously identified by random sequence peptide phage display library analysis as a potential site of interaction with p47 phox (15). Consistent with this observation, synthetic peptides derived from residues 86 -102 have been shown to inhibit superoxide production in the cell-free superoxide assay (15,17) and in electropermeabilized neutrophils (32), and can block the translocation of p47 phox and p67 phox to flavocytochrome b 558 in a cell-free system (17). In this study, we used site-directed mutagenesis to probe the role of specific charged amino acid residues within this region of gp91 phox , hypothesizing that electrostatic interactions between charged residues in gp91 phox and p47 phox may be important for assembly of the active oxidase complex.…”

Section: Discussionsupporting

confidence: 53%

Mutagenesis of an Arginine- and Lysine-rich Domain in the gp91 Subunit of the Phagocyte NADPH-oxidase Flavocytochromeb 558

Biberstine-Kinkade¹,

Yu²,

Dinauer

1999

Journal of Biological Chemistry

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Section: Discussionsupporting

confidence: 53%

Mutagenesis of an Arginine- and Lysine-rich Domain in the gp91 Subunit of the Phagocyte NADPH-oxidase Flavocytochromeb 558

Biberstine-Kinkade¹,

Yu²,

Dinauer

1999

Journal of Biological Chemistry

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“…PMNs were electroporated on ice using two discharges of a 25-F capacitor at 1.75 to 2.5 kV/cm with a Gene Pulser II (Bio-Rad Laboratories, Hercules, CA) as described previously (DeLeo et al, 1996). Analysis of aliquots of the cells for trypan blue exclusion indicated 96 to 98% of the cells were permeabilized.…”

Section: Methodsmentioning

confidence: 99%

Nicotinamide Glycolates Antagonize CXCR2 Activity through an Intracellular Mechanism

Maeda¹,

Quinn²,

Schepetkin³

et al. 2009

J Pharmacol Exp Ther

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The chemokine receptors CXCR1/2 are involved in a variety of inflammatory diseases, including chronic obstructive pulmonary disease. Several classes of allosteric small-molecule CXCR1/2 antagonists have been developed. The data presented here describe the cellular pharmacology of the acid and ester forms of the nicotinamide glycolate pharmacophore, a potent antagonist of CXCR2 signaling by the chemokines CXCL1 and CXCL8. H acid was not internalized by neutrophils but was sufficient alone to inhibit CXCL1-stimulated calcium flux in neutrophils that were permeabilized by electroporation to permit its direct access to the cell interior. Neutrophil efflux of the acid was probenecid-sensitive, consistent with an organic acid transporter. These data support a mechanism wherein the nicotinamide glycolate ester serves as a lipophilic precursor that efficiently translocates into the intracellular neutrophil space to liberate the active acid form of the pharmacophore, which then acts at an intracellular site. Rapid inactivation by plasma esterases precluded use in vivo, but the mechanism elucidated provided insight for new nicotinamide pharmacophore classes with therapeutic potential.Chemoattractant cytokines, or chemokines, promote the directed migration of polymorphonuclear leukocytes (PMNs) to sites of inflammation in a process known as chemotaxis. Among the most important chemokines released during inflammatory responses are the "Cys-XaaCys" (CXC) or ␣ chemokines, which are characterized by the presence of an intervening amino acid between con-

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“…Superoxide assays were performed as described previously by measuring SOD-inhibitable reduction of ferricytochrome c [36,37] but with several modifications. Briefly, 0.5 ϫ 10 6 THP-1 cells were differentiated overnight with 10 ng/ml (1.6 nM) PMA.…”

Section: Superoxide Assaymentioning

confidence: 99%

Monocyte p110α phosphatidylinositol 3-kinase regulates phagocytosis, the phagocyte oxidase, and cytokine production

Lee

Nauseef

Moeenrezakhanlou

et al. 2007

Journal of Leukocyte Biology

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Mononuclear phagocytes are critical modulators and effectors of innate and adaptive immune responses, and PI-3Ks have been shown to be multifunctional monocyte regulators. The PI-3K family includes eight catalytic isoforms, and only limited information is available about how these contribute to fine specificity in monocyte cell regulation. We examined the regulation of phagocytosis, the phagocyte oxidative burst, and LPSinduced cytokine production by human monocytic cells deficient in p110␣ PI-3K. We observed that p110␣ PI-3K was required for phagocytosis of IgG-opsonized and nonopsonized zymosan in differentiated THP-1 cells, and the latter was inhibitable by mannose. In contrast, p110␣ PI-3K was not required for ingestion serum-opsonized zymosan. Taken together, these results suggest that Fc␥R-and mannose receptor-mediated phagocytosis are p110␣-dependent, whereas CR3-mediated phagocytosis involves a distinct isoform. It is notable that the phagocyte oxidative burst induced in response to PMA or opsonized zymosan was also found to be dependent on p110␣ in THP-1 cells. Furthermore, p110␣ was observed to exert selective and bidirectional effects on the secretion of pivotal cytokines. Incubation of p110␣-deficient THP-1 cells with LPS showed that p110␣ was required for IL-12p40 and IL-6 production, whereas it negatively regulated the production of TNF-␣ and IL-10. Cells deficient in p110␣ also exhibited enhanced p38 MAPK, JNK, and NF-B phosphorylation. Thus, p110␣ PI-3K appears to uniquely regulate important monocyte functions, where other PI-3K isoforms are uninvolved or unable to fully compensate. J. Leukoc. Biol. 81: 1548 -1561; 2007.

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Characterization of peptide diffusion into electropermeabilized neutrophils

Cited by 24 publications

References 64 publications

Mutagenesis of an Arginine- and Lysine-rich Domain in the gp91 Subunit of the Phagocyte NADPH-oxidase Flavocytochromeb 558

Mutagenesis of an Arginine- and Lysine-rich Domain in the gp91 Subunit of the Phagocyte NADPH-oxidase Flavocytochromeb 558

Nicotinamide Glycolates Antagonize CXCR2 Activity through an Intracellular Mechanism

Monocyte p110α phosphatidylinositol 3-kinase regulates phagocytosis, the phagocyte oxidase, and cytokine production

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