, Volume 16, Issue 1, pp 57–68 | Cite as

Effects of combination of tumor necrosis factor alpha and chemotactic peptide, f-met-leu-phe, on phagocytosis of opsonized microspheres by human neutrophils

  • James D. Ogle
  • J. Greg Noel
  • R. Michael Sramkoski
  • Cora K. Ogle
  • J. Wesley Alexander
Original Articles


Pretreatment of normal, human neutrophils with 8 units/ml of TNF-α followed by treatment with 10−8 M FMLP resulted in a synergistic effect of the combination of the two mediators on the enhancement of the phagocytic capacity of the cells. This enhancement of phagocytosis occurred without an additional increase in the upregulation of C3b receptors (CR1) beyond that caused by each mediator alone. Pretreatment of the cells with 8 units/ml of TNF-α followed by 10−6 M FMLP resulted in an additive effect of the mediators on neutrophil phagocytosis, again without an additional up-regulation of CR1. This additive effect resulted in an increase in phagocytic capacity of the neutrophils greater than that obtained by treatment of the cells with 10−6 M FMLP alone, which heretofore has resulted in the greatest enhancement of phagocytic capacity obtained by any pretreatment condition. These synergistic and additive effects of the combination of mediators could be of great importance in host defense against bacterial infections and have important implications regarding the mechanisms of receptor upregulation and phagocytosis.


Peptide Tumor Necrosis Tumor Necrosis Factor Synergistic Effect Important Implication 
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  1. 1.
    Ogle, J. D., J. G. Noel, C. K. Ogle, R. M. Sramkoski, andJ. W. Alexander. 1990. Effects of chemotactic peptide f-met-leu-phe (FMLP) on C3b receptor (CR1) expression and phagocytosis by human neutrophils.Inflammation 14:337–353.Google Scholar
  2. 2.
    Ogle, J. D., J. G. Noel, R. M. Sramkoski, C. K. Ogle, andJ. W. Alexander. 1990. The effects of cytokines, platelet activating factor, and arachidonate metabolites on C3b receptor (CR1, CD35) expression and phagocytosis by neutrophils.Cytokine 2:447–455.Google Scholar
  3. 3.
    Crouch, S., andJ. Fletcher. 1991. The priming effects of the products of stimulated mono nuclear cells on the response of neutrophils to C5a des arg.Br. J. Haematol. 77:158–164.Google Scholar
  4. 4.
    Kurtz, R. S., K. M. Young, andC. J. Czuprynski. 1989. Separate and combined effects of recombinant interleukin-lα and gamma interferon on antibacterial resistance.Infect. Immun. 57:553–558.Google Scholar
  5. 5.
    Berkow, R. L., andM. R. Dodson. 1988. Biochemical mechanisms involved in the priming of neutrophils by tumor necrosis factor.J. Leukocyte Biol. 44:345–352.Google Scholar
  6. 6.
    Tennenberg, S. D., andJ. S. Solomkin. 1990. Activation of neutrophils by cachectin/tumor necrosis factor: Priming ofN-formyl-methionyl-leucyl-phenylalanine-induced oxidative responsiveness via receptor mobilization without degranulation.J. Leukocyte Biol. 47:217–223.Google Scholar
  7. 7.
    Humbert, J. R., andE. L. Winsor. 1990. Tumor necrosis factor primes neutrophils by shortening the lag period of the respiratory burst.Am. J. Med. Sci. 300:209–213.Google Scholar
  8. 8.
    Atkinson, Y. H., W. A. Marasco, A. F. Lopez, andM. A. Vadas. 1988. Recombinant human tumor necrosis factor-α. Regulation ofN-formylmethionylleucylphenylalanine receptor affinity and function on human neutrophils.J. Clin. Invest. 81:759–765.Google Scholar
  9. 9.
    Yuo, A., S. Kitagawa, L Suzuki, A. Urabe, T. Okabe, M. Saito, andF. Takaku. 1989. Tumor necrosis factor as an activator of human granulocytes. Potentiation of the metabolisms triggered by the Ca2+-mobilizingagonists.J. Immunol. 142:1678–1684.Google Scholar
  10. 10.
    Renesto, P. 1991. Tumor necrosis factor-α enhances platelet activation via cathepsin G released from neutrophils.J. Immunol. 146:2305–2309.Google Scholar
  11. 11.
    Bauldry, S. A., C. E. McCall, S. L. Cousart, andD. A. Bass. 1991. Tumor necrosis factor-α priming of phospnolipase A2 activation in human neutrophils.J. Immunol. 146:1277–1285.Google Scholar
  12. 12.
    Bauldry, S. A., D. A. Bass, S. L. Cousart, andC. E. McCall. 1991. Tumor necrosis factor a priming of phospholipase D in human neutrophils.J. Biol. Chem. 266:4173–4179.Google Scholar
  13. 13.
    She, Z.-W., M. D. Wewers, D. J. Herzyk, A. L. Sagone, andW. B. Davis. 1989. Tumor necrosis factor primes neutrophils for hypochlorous acid production.J. Physiol. 257:L338-L345.Google Scholar
  14. 14.
    Alexander, J. W., D. B. Windhorst, andR. A. Good. 1968. Improved tests for the evaluation of neutrophil function in human disease.J. Lab. Clin. Med. 72:136–148.Google Scholar
  15. 15.
    Ferrante, A., andY. H. Thong. 1978. A rapid one-step procedure for purification of mono-nuclear and poly-morphonuclear leukocytes for human blood using a modification of the Hypaque-Ficoll technique.J. Immunol. Methods 24:389–393.Google Scholar
  16. 16.
    Ogle, J. D., J. G. Noel, R. M. Sramkoski, C. K. Ogle andJ. W. Alexander. 1988. Phagocytosis of opsonized fluorescent microspheres by human neutrophils. A two-color flow cytometric method for the determination of attachment and ingestion.J. Immunol. Methods 115:17–29.Google Scholar
  17. 17.
    Ogle, J. D., C. K. Ogle, J. G. Noel, P. Hurtubise, andJ. W. Alexander. 1985. Studies on the binding of C3b-coated microspheres to human neutrophils.J. Immunol. Methods 76:47–62.Google Scholar
  18. 18.
    Offner, F., D. PhilippÉ, D. Vogelaers, F. Colardyn, G. Baele, M. Baudrihaye, A. Vermeulen, andG. Leroux-Roels. 1990. Serum tumor necrosis factor levels in patients with infectious disease and septic shock.J. Lab. Clin. Med. 116:100–105.Google Scholar
  19. 19.
    Trautinger, F., A. F. Hammerle, G. Poschl, andM. Micksche. 1991. Respiratory burst capability of polymorphonuclear neutrophils and TNF-α serum levels in relationship to the development of septic syndrome in critically ill patients.J. Leukocyte Biol. 49:449–454.Google Scholar
  20. 20.
    Alexander, J. W., R. Dionigi, andJ. L. Meakins. 1971. Periodic variation in the antibacterial function of human neutrophils and its relationship to sepsis.Ann. Surg. 173:206–213.Google Scholar
  21. 21.
    Porteu, F., andC. Nathan. 1990. Shedding of tumor necrosis factor receptors by activated human neutrophils.J. Exp. Med. 172:599–607.Google Scholar

Copyright information

© Plenum Publishing Corporation 1992

Authors and Affiliations

  • James D. Ogle
    • 1
    • 3
  • J. Greg Noel
    • 3
  • R. Michael Sramkoski
    • 3
  • Cora K. Ogle
    • 2
    • 3
  • J. Wesley Alexander
    • 2
    • 3
  1. 1.Department of Molecular Genetics, Biochemistry and MicrobiologyUniversity of Cincinnati Medical CenterCincinnati
  2. 2.Department of SurgeryUniversity of Cincinnati Medical CenterCincinnati
  3. 3.Shriners Burns InstituteCincinnati

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