Effect of phorbol myristate acetate on the oxidative metabolism of human polymorphonuclear leukocytes

DeChatelet, Lawrence R.; Shirley, Pamela S.; Johnston, Richard B.

doi:10.1182/blood.v47.4.545.545

Cited by 316 publications

(69 citation statements)

References 18 publications

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“…First, lop6 M athrombin does not activate neutrophils as measured by generation of superoxide anion (Lai, unpublished observation). On the other hand, PMA (the positive control used in the present study; and Shasby et al, 1983) induces superoxide anion and hydrogen peroxide generation from neutrophils (Repine et al, 1974;De Chatelet et al, 1980). In the present study, PMA-activated neutrophils resulted in an increase in endothelial permeability.…”

Section: Discussionsupporting

confidence: 43%

“…(5 x lo5 cells) were layered on the endothelium for 10 minutes before the addition of thrombin. In another group of related experiments, neutrophils were added to the endothelial monolayer and were stimulated 10 minutes later with lo-' M phorbol 12-myristate 13-acetate (PMA) (Repine et al, 1974;De Chatelet et al, 1980). The PMA was dissolved in 1 mglml dimethyl sulfoxide and was subsequent diluted in PBS to a final concentration of 200 nglml.…”

Section: Experimental Designmentioning

confidence: 99%

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Thrombin‐induced increase in albumin permeability across the endothelium

Garcia

Siflinger-Birnboim

Bizios

et al. 1986

Journal Cellular Physiology

308

221

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We studied the effect of thrombin on albumin permeability across the endothelial monolayer in vitro. Bovine pulmonary artery endothelial cells were grown on micropore membranes. Morphologic analysis confirmed the presence of a confluent monolayer with interendothelial junctions. Albumin permeability was measured by the clearance of 125I-albumin across the endothelial monolayer. The control 125I-albumin clearance was 0.273 +/- 0.02 microliter/min. The native enzyme, alpha-thrombin (10(-6) to 10(-10) M), added to the luminal side of the endothelium produced concentration-dependent increases in albumin clearance (maximum clearance of 0.586 +/- 0.08 microliter/min at 10(-6) M). Gamma (gamma) thrombin (10(-6) M and 10(-8) M), which lacks the fibrinogen recognition site, also produced a concentration-dependent increase in albumin clearance similar to that observed with alpha-thrombin. Moreover, the two proteolytically inactive forms of the native enzyme, i-Pr2 P-alpha-thrombin and D-Phe-Pro-Arg-CH2-alpha-thrombin, increased the 125I-albumin clearance (0.610 +/- 0.09 microliter/min and 0.609 +/- 0.02 microliter/min for i-Pr2 P-alpha-thrombin and D-Phe-Pro-Arg-CH2-alpha-thrombin at 10(-6) M, respectively). Since the modified forms of thrombin lack the fibrinogen recognition and active serine protease sites, the results indicate that neither site is required for increased albumin permeability. The increase in albumin clearance with alpha-thrombin was not secondary to endothelial cell lysis because lactate dehydrogenase concentration in the medium following thrombin was not significantly different from baseline values. There was also no morphological evidence of cell lysis. Moreover, the increase in 125I-albumin clearance induced by alpha-thrombin was reversible by washing thrombin from the endothelium. The basis for the increased albumin permeability following the addition of alpha-thrombin appears to be a reversible change in endothelial cell shape with formation of intercellular gaps.

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Section: Discussionsupporting

confidence: 43%

Section: Experimental Designmentioning

confidence: 99%

Thrombin‐induced increase in albumin permeability across the endothelium

Garcia

Siflinger-Birnboim

Bizios

et al. 1986

Journal Cellular Physiology

308

221

View full text Add to dashboard Cite

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“…Activation of the oxidase through binding of soluble ligands (i.e., fMLP) to surface receptors usually results in O 2 production lasting less than 5 min, whereas receptor-independent activation (i.e., PMA) causes prolonged generation of the O 2 until depletion of necessary substrates and cofactors [332]. Furthermore, in intact cells, the activated oxidase is experiencing a continuous process of activation and deactivation [333].…”

Section: Membranementioning

confidence: 99%

“…PMA has become the most commonly used positive control for oxidase activation [332,338]; however, it is a nonphysiological stimulus. Originally considered to be involved in tumor promotion, although by themselves were not carcinogenic, phorbol esters resulted in many genetic and phenotypic changes, including an increase in oxidase production and the copurification of PKC with the putative phorboid receptor [339 -343].…”

Section: Membranementioning

confidence: 99%

Structural organization of the neutrophil NADPH oxidase: phosphorylation and translocation during priming and activation

Sheppard

Kelher

Moore

et al. 2005

Journal of Leukocyte Biology

330

275

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The reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is part of the microbicidal arsenal used by human polymorphonuclear neutrophils (PMNs) to eradicate invading pathogens. The production of a superoxide anion (O2-) into the phagolysosome is the precursor for the generation of more potent products, such as hydrogen peroxide and hypochlorite. However, this production of O2- is dependent on translocation of the oxidase subunits, including gp91phox, p22phox, p47phox, p67phox, p40phox, and Rac2 from the cytosol or specific granules to the plasma membrane. In response to an external stimuli, PMNs change from a resting, nonadhesive state to a primed, adherent phenotype, which allows for margination from the vasculature into the tissue and chemotaxis to the site of infection upon activation. Depending on the stimuli, primed PMNs display altered structural organization of the NADPH oxidase, in that there is phosphorylation of the oxidase subunits and/or translocation from the cytosol to the plasma or granular membrane, but there is not the complete assembly required for O2- generation. Activation of PMNs is the complete assembly of the membrane-linked and cytosolic NADPH oxidase components on a PMN membrane, the plasma or granular membrane. This review will discuss the individual components associated with the NADPH oxidase complex and the function of each of these units in each physiologic stage of the PMN: rested, primed, and activated.

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“…Hasui et al reported that a positive correlation exists between phagocytosis and H 2 O 2 production following ingestion of S. aureus [27]. PMA is known to directly activate protein kinase C, bypassing the process of phagocytosis [32]. When stimulated with PMA, addition of IgG did not have any appreciable effect on H 2 O 2 production with PMN of both mature and premature neonates.…”

Section: Discussionmentioning

confidence: 99%

Effect of immunoglobulin therapy on phagocytosis by polymorphonuclear leucocytes in whole blood of neonates

Fujiwara

Taniuchi

Hattori

et al. 1997

Clinical and Experimental Immunology

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SUMMARYThere has been some disagreement as to the clinical effect of intravenous immunoglobulin (IVIG) therapy on neonatal bacterial infections. We therefore evaluated the effect of IVIG therapy on neonatal polymorphonuclear leucocyte (PMN) functions by monitoring phagocytosis and hydrogen peroxide (H 2 O 2 ) production. Subjects were 10 mature neonates who had normal plasma levels (i.e. equal to adult plasma levels) of IgG and nine premature neonates who had lower plasma levels of IgG. Phagocytosis by PMN was measured using flow cytometric analysis of whole blood. Addition of g-globulin to the whole blood of mature neonates increased phagocytosis, but not significantly. Higher doses of added g-globulin (> 2·0 mg/ml, the concentration was expressed as that in the final reaction volume) decreased phagocytosis to under baseline level. In premature neonates addition of g-globulin increased phagocytosis and the significant maximum effect was observed with 0·5 mg/ml of the additional g-globulin.Higher doses of additional g-globulin (2·5 mg/ml) decreased phagocytosis to baseline level. Phagocytosis in four mature and four premature neonates was compared before and after 1 g/kg of IVIG therapy. Phagocytosis in mature neonates after IVIG therapy did not change compared with the pretreatment level. On the other hand, phagocytosis in premature neonates after IVIG therapy significantly increased compared with its pretreatment level. In both mature and premature neonates H 2 O 2 production following phagocytosis varied in parallel with changes of phagocytosis. The patterns of H 2 O 2 production following phagocytosis were essentially similar to those observed with phagocytosis. The above results are expected to form the basis for a rational indication for IVIG therapy against bacterial infections in neonates with low plasma IgG levels.

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Effect of phorbol myristate acetate on the oxidative metabolism of human polymorphonuclear leukocytes

Cited by 316 publications

References 18 publications

Thrombin‐induced increase in albumin permeability across the endothelium

Thrombin‐induced increase in albumin permeability across the endothelium

Structural organization of the neutrophil NADPH oxidase: phosphorylation and translocation during priming and activation

Effect of immunoglobulin therapy on phagocytosis by polymorphonuclear leucocytes in whole blood of neonates

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