Endotoxin Primes Human Neutrophils for Enhanced Production of Leukotriene B4

Docrfler, Martin E.; Danncr, Robert L.; Shclhamer, James H.; Moss, Joel; Parrillo, Joseph E.

doi:10.1097/00003246-198804000-00113

Cited by 2 publications

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The involvement of PLA 2 in primed stimulation is well documented. The enzyme appears to play a role in priming by diacyl-and alkylacylglycarol, inflammatory cytokines, and LPS (2,3,8,12,15,27,41). We were unable to detect appreciable concentrations of cytokines in the fluids employed in this study.…”

Section: Discussionmentioning

confidence: 58%

“…Such an observation may not be considered unusual since the patients that we chose were not suffering infection at the time of dialysis. Our observation that only challenge with PMA results in elevated LTB 4 release from PDE-primed PMN is reminiscent of LPS priming (14,15). However, the concentrations of endotoxin in the effluents used were below those required for priming (14), and unlike LPS, PDE-mediated priming of the oxidase is immediate with no requirement for incubation (10).…”

Section: Discussionmentioning

confidence: 70%

See 1 more Smart Citation

Role of Arachidonic Acid and Its Metabolites in the Priming of NADPH Oxidase in Human Polymorphonuclear Leukocytes by Peritoneal Dialysis Effluent

Daniels¹,

Lindsay²,

Keany³

et al. 1998

Clin Diagn Lab Immunol

View full text Add to dashboard Cite

Peritoneal dialysis effluent (PDE) contains a low-molecular-weight solute that will activate and prime the NADPH oxidase of human neutrophils via a phospholipase A2(PLA2)-dependent mechanism. Since the products of PLA2 are known to activate and prime the oxidase we have investigated their role in the dialysis effluent-mediated activation and priming of human neutrophils. NADPH oxidase activity of PDE-primed and -unprimed neutrophils was measured by lucigenin-enhanced chemiluminescence in the presence of known inhibitors of the arachidonic acid cascade. Incubation of neutrophils with the nonselective PLA2 inhibitor quinacrine (0 to 100 μM) reduced oxidase activity in both primed and unprimed cells. Furthermore, primed cells were more sensitive to the action of quinacrine than were unprimed cells. We were unable to determine the relative roles of secretory PLA2(sPLA2) and cytosolic PLA2(cPLA2) since the selectivesPLA2 inhibitor scalaradial (0 to 100 μM) inhibited oxidase activity in both groups of cells by similar degrees, while the specific cPLA2 inhibitor AACO-CF3 (0 to 50 μM) failed to affect activity in either group. Inhibition of platelet-activating factor (PAF), cycloxygenase, and 5-lipoxygenase-activating protein by hexanolamino-PAF (0 to 25 μM), flurbiprofen (0 to 25 μM), and MK886 (0 to 5 μM), respectively, had no effect upon oxidase activity. However, the direct inhibition of 5-lipoxygenase by caffeic acid or lipoxin A4resulted in a similar concentration-dependent attenuation of oxidase activity in both primed and unprimed cells. Leukotriene B4(LTB4) release from primed neutrophils was comparable to that from unprimed cells with the exception of phorbol myristate acetate-stimulated cells, which released fivefold more LTB4than control. Taken together, these results suggest that it is arachidonic acid per se, and not its metabolites, that is important in priming of the neutrophil NADPH oxidase by dialysis effluent.

show abstract