Killing of Gram-Negative Bacteria by Neutrophils: Role of O2- Independent System in Intracellular Killing and Evidence of O2-Dependent Extracellular Killing

  • Jerrold Weiss
  • Michael Victor
  • Linda Kao
  • Peter Elsbach
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 187)


The cytotoxic capabilities of the neutrophil have long been recognized, particularly in relation to this cell’s function against invading microorganisms (1). Two events central to the mobilization of the cytotoxic function of the neutrophil are: 1) the respiratory burst, a prompt and marked rise in O2 consumption generating, de novo, several toxic metabolites of reduced O2 (2); and 2) degranulation, the fusion of cytoplasmic granules with plasma membrane sites proximate to the target delivering pre-existing cytotoxic proteins into the space surrounding the microbe (3). Both granule proteins and O2 metabolites can be released outside the neutrophil and damage extracellular tissues and large non-ingested cells and parasites (4). However, substantial extracellular killing of bacteria has not been found under normal circumstances. Hence, it is generally believed that intracellular sequestration of the bacterium is required for effective killing by neutrophils (5).


Outer Membrane Respiratory Burst Bacterial Killing Intracellular Killing Hexose Monophosphate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1).
    Metchnikoff, E. “Lectures on the Comparable Pathology of Inflammation” (translated by F.A. Starling and E.H. Starling) Kegan, Paul, Trench, Truber, London (1893).Google Scholar
  2. 2).
    Babior, B.M. O2-independent microbial killing by phagocytes. New Eng. J. Med. 298:659 (1978).PubMedCrossRefGoogle Scholar
  3. 3).
    Hirsch, J.G. and Z.A. Cohn. Degranulation of polymorphonuclear leukocytes following phagocytosis of microorganisms. J. Exp. Med. 112:1005 (1960).PubMedCrossRefGoogle Scholar
  4. 4).
    Clark, R.A. Extracellular effects of the myeloperoxidase- hydrogen peroxide-halide system. Adv. Inflamm. Re s. 5:107 (1983).Google Scholar
  5. 5).
    Densen, P. and G.L. Mandell. Gonococcal Interactions with polymorphonuclear neutrophils: Importance of the phagosome for bactericidal activity. J. Clin. Invest. 62:1161 (1978).PubMedCrossRefGoogle Scholar
  6. 6).
    Elsbach, P. On the interaction between phagocytes and microorganisms. N. Engl.J. Med. 289:846 (1973).PubMedCrossRefGoogle Scholar
  7. 7).
    Beckerdite, S., C. mooney, R. Franson, and P. Elsbach. Early and discrete changes in permeability of E.coli and certain other gram-negative bacteria during killing by granulocytes. J. Exp. Med. 140:396 (1974).PubMedCrossRefGoogle Scholar
  8. 8).
    Elsbach, P. and J. Weiss. A réévaluation of the roles of the O2-dependent and O2-independent microbial systems of phagocytes. Rev. Infect. Pis.5:843 (1983).CrossRefGoogle Scholar
  9. 9).
    Lugtenberg, B. and L. van Alphen. Molecular architecture and functioning of the outer membrane of Escherichia coli and other gram-negative bacteria. Biochim. Biophys. Acta 737:51 (1983).PubMedCrossRefGoogle Scholar
  10. 10).
    Schindler, M. and M.J. Osborn. Interaction of divalent cations and polymixin B with lipopolysaccharide. Biochemistry 18:4425 (1979).PubMedCrossRefGoogle Scholar
  11. 11).
    Leive, L. The barrier function of the gram-negative bacterial envelope. Ann. N.Y. Acad. Sci. 235:109 (1974).PubMedCrossRefGoogle Scholar
  12. 12).
    Weiss, J., S. Beckerdite-Quagliata, and P. Elsbach. Resistance of gram-negative bacteria to purified bactericidal leukocyte proteins. Relation to binding and bacterial lipopolysaccharide structure. J. Clin. Invest. 65:619 (1980).PubMedCrossRefGoogle Scholar
  13. 13).
    Weiss, J., M. Victor, and P. Elsbach. Role of charge and hydrophobic interactions in the action of the bactericidal permeabilityOincreasing protein of neutrophils on gram-negative bacteria. J. Clin. Invest. 71:540 (1983).PubMedCrossRefGoogle Scholar
  14. 14).
    Weissl J., K. Muello, M. Victor, and P. Elsbach. The role of lipopolysaccharides in the action of the neutrophil bactericidal/ permeability-increaing protein on the bacterial envelope. J. Immunol. 132:3109 (1984.Google Scholar
  15. 15).
    Weiss, J., S. Beckerdite-Quagliata, and P. Elsbach. Determinants of the action of phospholipases A on the envelope phospholipids of Escherichia coli. J. Biol. Chem. 254:10010 (1979)Google Scholar
  16. 16).
    Weiss, J., K. Schmeidler, R. C. Franson, S. Beckerdite-Quagliata, and P. Elsbach. Reversible envelope effects during and after killing of Escherichia coli by a highly purified rabbit polymorphonuclear leukocyte fraction. Biochim. Biophys. Acta 436: 154 (1976).CrossRefGoogle Scholar
  17. 17).
    Weiss, J., M. Victor, D. Stendahl, and P. Elsbach. Killing of gram-negative bacteria by polymorphonuclear leukocytes. Role of an O2-independent bactericidal system. J. Clin. Invest. 69:959 (1982).PubMedCrossRefGoogle Scholar
  18. 18).
    Okamura, N. and J.K. Spitznagel. Outer membrane mutants of Salmonella typhimurium LT-2 have lipopolysaccharide-dependent resistance to bactericidal activity of anaerobic human neutrophils. Infect. Immun. 36:1086 (1982).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • Jerrold Weiss
    • 1
    • 2
  • Michael Victor
    • 1
    • 2
  • Linda Kao
    • 1
    • 2
  • Peter Elsbach
    • 1
    • 2
  1. 1.Department of MedicineNew York University School of MedicineNew YorkUSA
  2. 2.Department of MicrobiologyNew York University School of MedicineNew YorkUSA

Personalised recommendations