Home LiteratureArticle Details
PMID: 2537852 Published · ppublish English Journal Article

Bacterial lipopolysaccharides prime human neutrophils for enhanced production of leukotriene B4.

The Journal of clinical investigation ·Vol. 83 ·No. 3 ·1989-03-00 ·Pages 970-7

Doerfler ME, Danner RL, Shelhamer JH, Parrillo JE

Abstract

Neutrophils can be "primed" for an enhanced respiratory burst by lipopolysaccharide (LPS) in concentrations measurable in patients with septic shock. Leukotriene B4 (LTB4) is the primary eicosanoid product of neutrophils and is felt to be a mediator of host defense and inflammation. We investigated the in vitro effects of LPS on neutrophil production of LTB4 and the omega-oxidation metabolites of LTB4. Incubation of neutrophils with LPS in concentrations ranging from 0.01 to 100 ng/ml did not result in production of LTB4 or metabolites in the absence of a second stimulus. Priming neutrophils with LPS and then stimulating with opsonized zymosan, phorbol-myristate-acetate or a low concentration of the calcium ionophore A23187 resulted in enhanced production of LTB4. LPS priming of neutrophils occurred in a concentration dependent manner. LPS did not result in LTB4 production in response to the chemoattractant peptide FMLP. LPS priming of neutrophils had no effect on cytosolic calcium concentrations of resting or zymosan-stimulated cells. These results suggest that LPS might effect host defense and tissue injury by potentiating the effect of other stimulants on neutrophil production of LTB4. This LPS induced enhancement may represent an important pathogenetic pathway in patients with gram negative sepsis.

MeSH Terms
Calcimycin/pharmacology Calcium/blood Cytosol/metabolism Humans Kinetics Leukotriene B4/blood Lipopolysaccharides/pharmacology N-Formylmethionine Leucyl-Phenylalanine/pharmacology Neutrophils/drug effects,metabolism Opsonin Proteins Oxidation-Reduction Salmonella Tetradecanoylphorbol Acetate/pharmacology Zymosan/pharmacology
Chemicals
Lipopolysaccharides Opsonin Proteins Leukotriene B4 Calcimycin N-Formylmethionine Leucyl-Phenylalanine Zymosan Tetradecanoylphorbol Acetate Calcium
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Doerfler M E
Critical Care Medicine Department, National Institutes of Health, Bethesda, Maryland 20892.
Danner R L
Shelhamer J H
Parrillo J E
References (53)
53 references, click to expand
  1. Lack of correlation between calcium mobilization and respiratory burst activation induced by chemotactic factors in rabbit polymorphonuclear leukocytes.
    Biochem Biophys Res Commun. 1987 Apr 29;144(2):794-800 PMID: 3034265
  2. Phorbol myristate acetate and the calcium ionophore A23187 synergistically induce release of LTB4 by human neutrophils: involvement of protein kinase C activation in regulation of the 5-lipoxygenase pathway.
    J Immunol. 1987 May 15;138(10):3396-402 PMID: 3033073
  3. Leukotrienes and the pulmonary microcirculation.
    Am Rev Respir Dis. 1987 Jul;136(1):161-9 PMID: 3037955
  4. Inhibition of endotoxin-induced priming of human neutrophils by lipid X and 3-Aza-lipid X.
    J Clin Invest. 1987 Sep;80(3):605-12 PMID: 3624479
  5. Serial cardiovascular variables in survivors and nonsurvivors of human septic shock: heart rate as an early predictor of prognosis.
    Crit Care Med. 1987 Oct;15(10):923-9 PMID: 3652707
  6. Temporal association of calcium mobilization, inositol trisphosphate generation, and superoxide anion release by human neutrophils activated by serum opsonized and nonopsonized particulate stimuli.
    Biochem Biophys Res Commun. 1988 Jan 29;150(2):532-9 PMID: 2829878
  7. Stimulus-dependent myristoylation of a major substrate for protein kinase C.
    Nature. 1988 Mar 24;332(6162):362-4 PMID: 3352735
  8. STUDIES ON TUBERCULIN FEVER. 3. MECHANISMS INVOLVED IN THE RELEASE OF ENDOGENOUS PYROGEN IN VITRO.
    J Exp Med. 1965 Aug 1;122:207-35 PMID: 14316942
  9. Detection of endotoxin in the blood of patients with sepsis due to gram-negative bacteria.
    N Engl J Med. 1970 Dec 10;283(24):1313-6 PMID: 5478453
  10. Measurement of prostaglandins, thromboxanes, prostacyclin and their metabolites by gas liquid chromatography--mass spectrometry.
    Adv Prostaglandin Thromboxane Res. 1978;5:39-94 PMID: 364961
  11. Transformation of arachidonic acid by rabbit polymorphonuclear leukocytes. Formation of a novel dihydroxyeicosatetraenoic acid.
    J Biol Chem. 1979 Apr 25;254(8):2643-6 PMID: 429307
  12. Chemoattractants stimulate degradation of methylated phospholipids and release of arachidonic acid in rabbit leukocytes.
    Proc Natl Acad Sci U S A. 1979 Jun;76(6):2640-3 PMID: 288052
  13. Leukotriene B, a potent chemokinetic and aggregating substance released from polymorphonuclear leukocytes.
    Nature. 1980 Jul 17;286(5770):264-5 PMID: 6250050
  14. The human PMN leukocyte chemotactic activity of complex hydroxy-eicosatetraenoic acids (HETEs).
    J Immunol. 1980 Oct;125(4):1789-91 PMID: 7410854
  15. Control of vascular permeability by polymorphonuclear leukocytes in inflammation.
    Nature. 1981 Feb 19;289(5799):646-50 PMID: 7464931
  16. Release and metabolism of arachidonic acid in human neutrophils.
    J Biol Chem. 1981 Jul 25;256(14):7228-34 PMID: 6788763
  17. Transformation of arachidonic acid in leukocytes. Isolation and structural analysis of a novel dihydroxy derivative.
    Prostaglandins Med. 1981 Jun;6(6):557-70 PMID: 6267638
  18. Stimulation of human leukocyte degranulation by leukotriene B4 and its omega-oxidized metabolites.
    FEBS Lett. 1981 Dec 21;136(1):141-4 PMID: 6274698
  19. Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters.
    J Biol Chem. 1982 Jul 10;257(13):7847-51 PMID: 7085651
  20. Increase in vascular permeability induced by leukotriene B4 and the role of polymorphonuclear leukocytes.
    Inflammation. 1982 Jun;6(2):189-200 PMID: 6179872
  21. Modulation of the development of cell-mediated immunity: possible role of the products of the cyclo-oxygenase and the lipoxygenase pathways of arachidonic acid metabolism.
    Int J Immunopharmacol. 1982;4(3):195-204 PMID: 6809647
  22. Leukotriene B4 induces human suppressor lymphocytes.
    Biochem Biophys Res Commun. 1982 Oct 29;108(4):1531-7 PMID: 6295385
  23. Phorbol esters increase the amount of Ca2+, phospholipid-dependent protein kinase associated with plasma membrane.
    Nature. 1983 Feb 17-23;301(5901):621-3 PMID: 6828143
  24. Phorbol 12-myristate 13-acetate activates rabbit neutrophils without an apparent rise in the level of intracellular free calcium.
    Biochem Biophys Res Commun. 1983 Jul 29;114(2):638-45 PMID: 6411090
  25. Release of leukotriene B4 from human neutrophils and its relationship to degranulation induced by N-formyl-methionyl-leucyl-phenylalanine, serum-treated zymosan and the ionophore A23187.
    Immunology. 1983 Sep;50(1):65-73 PMID: 6309653
  26. Lipoxygenase pathways.
    Br Med Bull. 1983 Jul;39(3):219-22 PMID: 6313113
  27. Immunoregulatory activity of metabolites of arachidonic acid and their role in inflammation.
    Br Med Bull. 1983 Jul;39(3):243-8 PMID: 6313115
  28. Inhibition of phospholipase.
    Br Med Bull. 1983 Jul;39(3):260-4 PMID: 6354351
  29. Differential activation of phosphatidylinositol deacylation and a pathway via diphosphoinositide in macrophages responding to zymosan and ionophore A23187.
    J Biol Chem. 1984 Mar 10;259(5):3111-6 PMID: 6321496
  30. Human pulmonary macrophage-derived mucus secretagogue.
    J Exp Med. 1984 Mar 1;159(3):844-60 PMID: 6699545
  31. Stimulus response coupling in the human neutrophil. I. Kinetic analysis of changes in calcium permeability.
    J Biol Chem. 1984 Apr 10;259(7):4070-5 PMID: 6323454
  32. Stimulus response coupling in the human neutrophil. II. Temporal analysis of changes in cytosolic calcium and calcium efflux.
    J Biol Chem. 1984 Apr 10;259(7):4076-82 PMID: 6323455
  33. The biologically active leukotrienes. Biosynthesis, metabolism, receptors, functions, and pharmacology.
    J Clin Invest. 1984 Apr;73(4):889-97 PMID: 6323538
  34. A potential second messenger role for unsaturated fatty acids: activation of Ca2+-dependent protein kinase.
    Science. 1984 May 11;224(4649):622-5 PMID: 6231726
  35. The activation of protein kinase C by biologically active lipid moieties of lipopolysaccharide.
    J Biol Chem. 1984 Aug 25;259(16):10048-52 PMID: 6236211
  36. Omega-oxidation is the major pathway for the catabolism of leukotriene B4 in human polymorphonuclear leukocytes.
    J Biol Chem. 1984 Aug 25;259(16):10181-7 PMID: 6088485
  37. Protein kinase C activation of physiological processes in human neutrophils at vanishingly small cytosolic Ca2+ levels.
    Nature. 1984 Aug 23-29;310(5979):691-3 PMID: 6236373
  38. Inositol trisphosphate, a novel second messenger in cellular signal transduction.
    Nature. 1984 Nov 22-28;312(5992):315-21 PMID: 6095092
  39. Priming of neutrophils for enhanced release of oxygen metabolites by bacterial lipopolysaccharide. Evidence for increased activity of the superoxide-producing enzyme.
    J Exp Med. 1984 Dec 1;160(6):1656-71 PMID: 6096475
  40. Intracellular retention of the 5-lipoxygenase pathway product, leukotriene B4, by human neutrophils activated with unopsonized zymosan.
    J Immunol. 1985 Apr;134(4):2624-30 PMID: 2982947
  41. Intracellular Ca2+ requirements for zymosan-stimulated phosphoinositide hydrolysis in mouse peritoneal macrophages.
    Biochem Biophys Res Commun. 1986 Jan 14;134(1):367-71 PMID: 3004439
  42. Analysis of leukotriene B4 in human lung lavage by HPLC and mass spectrometry.
    Prostaglandins. 1986 Feb;31(2):227-37 PMID: 3008216
  43. Abnormal neutrophil-pulmonary interaction in the adult respiratory distress syndrome. Qualitative and quantitative assessment of pulmonary neutrophil kinetics in humans with in vivo 111indium neutrophil scintigraphy.
    Am Rev Respir Dis. 1986 May;133(5):797-804 PMID: 3706888
  44. The role of leukotriene B4 in the genesis of oxygen toxicity in the lung.
    Am Rev Respir Dis. 1986 May;133(5):805-8 PMID: 3010781
  45. Bacterial lipopolysaccharides prime macrophages for enhanced release of arachidonic acid metabolites.
    J Exp Med. 1986 Jul 1;164(1):165-79 PMID: 2941513
  46. Studies and perspectives of protein kinase C.
    Science. 1986 Jul 18;233(4761):305-12 PMID: 3014651
  47. Bacterial lipopolysaccharides, phorbol myristate acetate, and zymosan induce the myristoylation of specific macrophage proteins.
    Proc Natl Acad Sci U S A. 1986 Aug;83(16):5817-21 PMID: 3461461
  48. The metabolism of phosphoinositide-derived messenger molecules.
    Science. 1986 Dec 19;234(4783):1519-26 PMID: 3024320
  49. Phospholipid metabolism in human neutrophils activated by N-formyl-methionyl-leucyl-phenylalanine. Degranulation is not required for release of arachidonic acid: studies with neutrophils and neutrophil-derived cytoplasts.
    Biochem J. 1986 Jun 15;236(3):829-37 PMID: 3790093
  50. Modulation by phorbol myristate acetate of arachidonic acid release and leukotriene synthesis by human polymorphonuclear leukocytes stimulated with A23187.
    Biochem Biophys Res Commun. 1986 Dec 15;141(2):399-404 PMID: 3026382
  51. The leukotriene B4 paradox: neutrophils can, but will not, respond to ligand-receptor interactions by forming leukotriene B4 or its omega-metabolites.
    Biochem J. 1987 Jan 1;241(1):55-62 PMID: 3032161
  52. A Ca2+-insensitive form of fura-2 associated with polymorphonuclear leukocytes. Assessment and accurate Ca2+ measurement.
    J Biol Chem. 1987 May 5;262(13):6308-12 PMID: 3571258
  53. Leukotriene B4 catabolism: quantitation of leukotriene B4 and its omega-oxidation products by reversed-phase high-performance liquid chromatography.
    Methods Enzymol. 1987;141:355-71 PMID: 3037248
Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI113983
Published
1989-03-00
Pages
970-7
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC303773
Subset
IM
External Links
PubMed source DOI: 10.1172/JCI113983 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2