Skip to main content
Infection and Immunity logoLink to Infection and Immunity
. 1992 Aug;60(8):3238–3243. doi: 10.1128/iai.60.8.3238-3243.1992

Pasteurella haemolytica leukotoxin enhances production of leukotriene B4 and 5-hydroxyeicosatetraenoic acid by bovine polymorphonuclear leukocytes.

P A Henricks 1, G J Binkhorst 1, A A Drijver 1, F P Nijkamp 1
PMCID: PMC257307  PMID: 1322370

Abstract

The influence of the leukotoxin of Pasteurella haemolytica on the generation of arachidonic acid metabolites by bovine polymorphonuclear leukocytes (PMNs) was investigated. PMNs released 5-, 12-, and 15-hydroxyeicosatetraenoic acids (5-, 12-, and 15-HETE) and leukotriene B4 (LTB4) upon stimulation with arachidonic acid. The leukotoxin preparations dose dependently enhanced the release of the 5-lipoxygenase products 5-HETE and LTB4 in arachidonic acid-stimulated PMNs, whereas the release of 12- and 15-HETE was not affected. The enhanced release of LTB4 and 5-HETE was not due to a decreased cellular retention of the 5-lipoxygenase products. In addition, leukotoxin preparations by themselves were also able to induce LTB4 and 5-HETE production in the absence of exogenous arachidonic acid. Generation of 5-lipoxygenase products by PMNs stimulated by leukotoxin may represent an important cellular event that occurs during infections with P. haemolytica.

Full text

PDF
3243

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Allan E. M., Gibbs H. A., Wiseman A., Selman I. E. Sequential lesions of experimental bovine pneumonic pasteurellosis. Vet Rec. 1985 Oct 26;117(17):438–442. doi: 10.1136/vr.117.17.438. [DOI] [PubMed] [Google Scholar]
  2. Baluyut C. S., Simonson R. R., Bemrick W. J., Maheswaran S. K. Interaction of Pasteurella haemolytica with bovine neutrophils: identification and partial characterization of a cytotoxin. Am J Vet Res. 1981 Nov;42(11):1920–1926. [PubMed] [Google Scholar]
  3. Berggren K. A., Baluyut C. S., Simonson R. R., Bemrick W. J., Maheswaran S. K. Cytotoxic effects of Pasteurella haemolytica on bovine neutrophils. Am J Vet Res. 1981 Aug;42(8):1383–1388. [PubMed] [Google Scholar]
  4. Bhakdi S., Greulich S., Muhly M., Eberspächer B., Becker H., Thiele A., Hugo F. Potent leukocidal action of Escherichia coli hemolysin mediated by permeabilization of target cell membranes. J Exp Med. 1989 Mar 1;169(3):737–754. doi: 10.1084/jem.169.3.737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bhakdi S., Mackman N., Nicaud J. M., Holland I. B. Escherichia coli hemolysin may damage target cell membranes by generating transmembrane pores. Infect Immun. 1986 Apr;52(1):63–69. doi: 10.1128/iai.52.1.63-69.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bremm K. D., König W., Pfeiffer P., Rauschen I., Theobald K., Thelestam M., Alouf J. E. Effect of thiol-activated toxins (streptolysin O, alveolysin, and theta toxin) on the generation of leukotrienes and leukotriene-inducing and -metabolizing enzymes from human polymorphonuclear granulocytes. Infect Immun. 1985 Dec;50(3):844–851. doi: 10.1128/iai.50.3.844-851.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Brunner C. J., George A. L., 3rd, Hsu C. L. Chemotactic response of bovine neutrophils to Pasteurella haemolytica culture fluid. Vet Immunol Immunopathol. 1989 Jul;21(3-4):279–292. doi: 10.1016/0165-2427(89)90037-8. [DOI] [PubMed] [Google Scholar]
  8. Cavalieri S. J., Snyder I. S. Effect of Escherichia coli alpha-hemolysin on human peripheral leukocyte function in vitro. Infect Immun. 1982 Sep;37(3):966–974. doi: 10.1128/iai.37.3.966-974.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chang Y. F., Renshaw H. W. Pasteurella haemolytica leukotoxin: comparison of 51chromium-release, trypan blue dye exclusion, and luminol-dependent chemiluminescence-inhibition assays for sensitivity in detecting leukotoxin activity. Am J Vet Res. 1986 Jan;47(1):134–138. [PubMed] [Google Scholar]
  10. Chang Y. F., Renshaw H. W., Richards A. B. Pasteurella haemolytica leukotoxin: physicochemical characteristics and susceptibility of leukotoxin to enzymatic treatment. Am J Vet Res. 1986 Apr;47(4):716–723. [PubMed] [Google Scholar]
  11. Clinkenbeard K. D., Mosier D. A., Confer A. W. Transmembrane pore size and role of cell swelling in cytotoxicity caused by Pasteurella haemolytica leukotoxin. Infect Immun. 1989 Feb;57(2):420–425. doi: 10.1128/iai.57.2.420-425.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Clinkenbeard K. D., Mosier D. A., Timko A. L., Confer A. W. Effects of Pasteurella haemolytica leukotoxin on cultured bovine lymphoma cells. Am J Vet Res. 1989 Feb;50(2):271–275. [PubMed] [Google Scholar]
  13. Engels F., Willems H., Nijkamp F. P. Cyclooxygenase-catalyzed formation of 9-hydroxylinoleic acid by guinea pig alveolar macrophages under non-stimulated conditions. FEBS Lett. 1986 Dec 15;209(2):249–253. doi: 10.1016/0014-5793(86)81121-8. [DOI] [PubMed] [Google Scholar]
  14. Ford-Hutchinson A. W., Bray M. A., Doig M. V., Shipley M. E., Smith M. J. Leukotriene B, a potent chemokinetic and aggregating substance released from polymorphonuclear leukocytes. Nature. 1980 Jul 17;286(5770):264–265. doi: 10.1038/286264a0. [DOI] [PubMed] [Google Scholar]
  15. Gadeberg O. V., Orskov I. In vitro cytotoxic effect of alpha-hemolytic Escherichia coli on human blood granulocytes. Infect Immun. 1984 Jul;45(1):255–260. doi: 10.1128/iai.45.1.255-260.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Goetzl E. J., Sun F. F. Generation of unique mono-hydroxy-eicosatetraenoic acids from arachidonic acid by human neutrophils. J Exp Med. 1979 Aug 1;150(2):406–411. doi: 10.1084/jem.150.2.406. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Grimminger F., Walmrath D., Birkemeyer R. G., Bhakdi S., Seeger W. Leukotriene and hydroxyeicosatetraenoic acid generation elicited by low doses of Escherichia coli hemolysin in rabbit lungs. Infect Immun. 1990 Aug;58(8):2659–2663. doi: 10.1128/iai.58.8.2659-2663.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Heidel J. R., Taylor S. M., Laegreid W. W., Silflow R. M., Liggitt H. D., Leid R. W. Characterization of arachidonic acid metabolism, superoxide production, and bacterial killing in bovine circulating neutrophils and elicited alveolar neutrophils. J Leukoc Biol. 1989 Jul;46(1):41–50. doi: 10.1002/jlb.46.1.41. [DOI] [PubMed] [Google Scholar]
  19. Henricks P. A., Binkhorst G. J., Drijver A. A., Van der Vliet H., Nijkamp F. P. The effect of Pasteurella haemolytica cytotoxin on bovine polymorphonuclear leukocytes can be attenuated by beta-adrenoceptor antagonists. Vet Microbiol. 1990 Apr;22(2-3):259–266. doi: 10.1016/0378-1135(90)90113-a. [DOI] [PubMed] [Google Scholar]
  20. Henricks P. A., Binkhorst G. J., Nijkamp F. P. Stress diminishes infiltration and oxygen metabolism of phagocytic cells in calves. Inflammation. 1987 Dec;11(4):427–437. doi: 10.1007/BF00915986. [DOI] [PubMed] [Google Scholar]
  21. Kaehler K. L., Markham R. J., Muscoplat C. C., Johnson D. W. Evidence of species specificity in the cytocidal effects of Pasteurella haemolytica. Infect Immun. 1980 Nov;30(2):615–616. doi: 10.1128/iai.30.2.615-616.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Keane W. F., Welch R., Gekker G., Peterson P. K. Mechanism of Escherichia coli alpha-hemolysin-induced injury to isolated renal tubular cells. Am J Pathol. 1987 Feb;126(2):350–357. [PMC free article] [PubMed] [Google Scholar]
  23. Lagarde M., Croset M., Boukhchache D., Greffe A., Dechavanne M., Renaud S. Lipoxygenase activity of intact human platelets. Prostaglandins Leukot Med. 1984 Jan;13(1):61–66. doi: 10.1016/0262-1746(84)90103-3. [DOI] [PubMed] [Google Scholar]
  24. Lo R. Y., Strathdee C. A., Shewen P. E. Nucleotide sequence of the leukotoxin genes of Pasteurella haemolytica A1. Infect Immun. 1987 Sep;55(9):1987–1996. doi: 10.1128/iai.55.9.1987-1996.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Maheswaran S. K., Berggren K. A., Simonson R. R., Ward G. E., Muscoplat C. C. Kinetics of interaction and fate of Pasteurella hemolytica in bovine alveolar macrophages. Infect Immun. 1980 Oct;30(1):254–262. doi: 10.1128/iai.30.1.254-262.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Martin T. R., Altman L. C., Albert R. K., Henderson W. R. Leukotriene B4 production by the human alveolar macrophage: a potential mechanism for amplifying inflammation in the lung. Am Rev Respir Dis. 1984 Jan;129(1):106–111. doi: 10.1164/arrd.1984.129.1.106. [DOI] [PubMed] [Google Scholar]
  27. McColl S. R., Krump E., Naccache P. H., Caon A. C., Borgeat P. Activation of the human neutrophil 5-lipoxygenase by exogenous arachidonic acid: involvement of pertussis toxin-sensitive guanine nucleotide-binding proteins. Br J Pharmacol. 1989 Aug;97(4):1265–1273. doi: 10.1111/j.1476-5381.1989.tb12588.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Raulf M., Alouf J. E., König W. Effect of staphylococcal delta-toxin and bee venom peptide melittin on leukotriene induction and metabolism of human polymorphonuclear granulocytes. Infect Immun. 1990 Aug;58(8):2678–2682. doi: 10.1128/iai.58.8.2678-2682.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Rehmtulla A. J., Thomson R. G. A review of the lesions in shipping fever of cattle. Can Vet J. 1981 Jan;22(1):1–8. [PMC free article] [PubMed] [Google Scholar]
  30. Scheffer J., König W., Hacker J., Goebel W. Bacterial adherence and hemolysin production from Escherichia coli induces histamine and leukotriene release from various cells. Infect Immun. 1985 Oct;50(1):271–278. doi: 10.1128/iai.50.1.271-278.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Seeger W., Suttorp N. Role of membrane lipids in the pulmonary vascular abnormalities caused by bacterial toxins. Am Rev Respir Dis. 1987 Aug;136(2):462–466. doi: 10.1164/ajrccm/136.2.462. [DOI] [PubMed] [Google Scholar]
  32. Shewen P. E., Wilkie B. N. Cytotoxin of Pasteurella haemolytica acting on bovine leukocytes. Infect Immun. 1982 Jan;35(1):91–94. doi: 10.1128/iai.35.1.91-94.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Shewen P. E., Wilkie B. N. Evidence for the Pasteurella haemolytica cytotoxin as a product of actively growing bacteria. Am J Vet Res. 1985 May;46(5):1212–1214. [PubMed] [Google Scholar]
  34. Sigal E., Grunberger D., Cashman J. R., Craik C. S., Caughey G. H., Nadel J. A. Arachidonate 15-lipoxygenase from human eosinophil-enriched leukocytes: partial purification and properties. Biochem Biophys Res Commun. 1988 Jan 15;150(1):376–383. doi: 10.1016/0006-291x(88)90531-1. [DOI] [PubMed] [Google Scholar]
  35. Slocombe R. F., Malark J., Ingersoll R., Derksen F. J., Robinson N. E. Importance of neutrophils in the pathogenesis of acute pneumonic pasteurellosis in calves. Am J Vet Res. 1985 Nov;46(11):2253–2258. [PubMed] [Google Scholar]
  36. Strathdee C. A., Lo R. Y. Extensive homology between the leukotoxin of Pasteurella haemolytica A1 and the alpha-hemolysin of Escherichia coli. Infect Immun. 1987 Dec;55(12):3233–3236. doi: 10.1128/iai.55.12.3233-3236.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Sun F. F., McGuire J. C. Metabolism of arachidonic acid by human neutrophils. Characterization of the enzymatic reactions that lead to the synthesis of leukotriene B4. Biochim Biophys Acta. 1984 Jun 6;794(1):56–64. doi: 10.1016/0005-2760(84)90297-2. [DOI] [PubMed] [Google Scholar]
  38. Suttorp N., Seeger W., Dewein E., Bhakdi S., Roka L. Staphylococcal alpha-toxin-induced PGI2 production in endothelial cells: role of calcium. Am J Physiol. 1985 Jan;248(1 Pt 1):C127–C134. doi: 10.1152/ajpcell.1985.248.1.C127. [DOI] [PubMed] [Google Scholar]
  39. Suttorp N., Seeger W., Zucker-Reimann J., Roka L., Bhakdi S. Mechanism of leukotriene generation in polymorphonuclear leukocytes by staphylococcal alpha-toxin. Infect Immun. 1987 Jan;55(1):104–110. doi: 10.1128/iai.55.1.104-110.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Taylor S. M., Liggitt H. D., Laegreid W. W., Silflow R., Leid R. W. Arachidonic acid metabolism in bovine alveolar macrophages. Effect of calcium ionophore on lipoxygenase products. Inflammation. 1986 Jun;10(2):157–165. doi: 10.1007/BF00915997. [DOI] [PubMed] [Google Scholar]
  41. Turk J., Maas R. L., Brash A. R., Roberts L. J., 2nd, Oates J. A. Arachidonic acid 15-lipoxygenase products from human eosinophils. J Biol Chem. 1982 Jun 25;257(12):7068–7076. [PubMed] [Google Scholar]
  42. Verhagen J., Walstra P., Veldink G. A., Vliegenthart J. F., Bruynzeel P. L. Separation and quantitation of leukotrienes by reversed-phase high-performance liquid chromatography. Prostaglandins Leukot Med. 1984 Jan;13(1):15–20. doi: 10.1016/0262-1746(84)90097-0. [DOI] [PubMed] [Google Scholar]
  43. Walstra P., Verhagen J., Vermeer M. A., Veldink G. A., Vliegenthart J. F. Demonstration of a 12-lipoxygenase activity in bovine polymorphonuclear leukocytes. Biochim Biophys Acta. 1987 Sep 25;921(2):312–319. doi: 10.1016/0005-2760(87)90032-4. [DOI] [PubMed] [Google Scholar]
  44. Williams J. D., Lee T. H., Lewis R. A., Austen F. Intracellular retention of the 5-lipoxygenase pathway product, leukotriene B4, by human neutrophils activated with unopsonized zymosan. J Immunol. 1985 Apr;134(4):2624–2630. [PubMed] [Google Scholar]
  45. van den Ingh T. S., Visser I. J., Henricks P. A., Binkhorst G. J. Pulmonary lesions induced by a Pasteurella haemolytica cytotoxin preparation in calves. Zentralbl Veterinarmed B. 1990 Jun;37(4):297–308. doi: 10.1111/j.1439-0450.1990.tb01062.x. [DOI] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES