Interactions Between Antibiotics, Phagocytes, and Bacteria

  • W. L. Hand
  • N. L. King-Thompson
  • T. H. Steinberg
  • D. L. Hand
Conference paper


Antibiotics have biological effects other than direct antimicrobial activity (i.e., other than growth inhibition or killing of organisms). We have been especially interested in the ability of antimicrobial agents to interact with phagocytes and to influence the fate of bacteria ingested by these cells. A major reason for this interest is that survival, and even multiplication, of pathogenic organisms after ingestion by phagocytes may lead to chronic or progressive disease [1,2]. Bacteria which fully exhibit this capability include Mycobacterium tuberculosis and Legionella pneumophila. To a lesser extent many bacteria, including Salmonella and Staphylococcus aureus, can manifest intraphagocytic survival. The efficacy of an antibiotic in therapy of infections, especially those due to facultative intracellular organisms, will depend upon both the extracellular drug-bacterial interaction and the capacity of the antibiotic to penetrate phagocytes and influence the functions of host cells and organisms. Thus, it is important to study the interactions between antibiotics, phagocytes, and bacteria in detail. In an effort to define certain of these interactions we have studied: the uptake of antimicrobial agents by various phagocytic cells, the mechanisms of this entry process for specific antibiotics, the effects of certain factors (phagocytosis, smoking) on drug uptake, the influence of antibiotics on survival of intraphagocytic bacteria, and the consequences of exposure to antibiotics on phagocyte oxidative metabolism.


Alveolar Macrophage Antimicrob Agent Phagocytic Cell Human Polymorphonuclear Leukocyte Human Alveolar Macrophage 
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.


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  1. 1.
    Horwitz MA (1982) Phagocytosis of microorganisms. Rev Infect Dis 4:104–123PubMedCrossRefGoogle Scholar
  2. 2.
    WHO Scientific Group (1973) Cell-mediated immunity and resistance to infection. Int Arch Allergy Appl Immunol 44:589–648Google Scholar
  3. 3.
    Johnson JD, Hand WL, Francis JB, King-Thompson NL, Corwin RW (1980) Antibiotic uptake by alveolar macrophages. J Lab Clin Med 95:429–439PubMedGoogle Scholar
  4. 4.
    Hand WL, Corwin RW, Steinberg TH, Grossman GD (1984) Uptake of antibiotics by human alveolar macrophages. Am Rev Respir Dis 129:933–937PubMedGoogle Scholar
  5. 5.
    Hand WL, Boozer RM, King-Thompson NL (1985) Antibiotic uptake by alveolar macrophages of smokers. Antimicrob Agents Chemother 27:42–45PubMedGoogle Scholar
  6. 6.
    Prokesch RC, Hand WL (1982) Antibiotic entry into human polymorphonuclear leukocytes. Antimicrob Agents Chemother 21:373–380PubMedGoogle Scholar
  7. 7.
    Boyum A (1976) Isolation of lymphocytes, granulocytes and macrophages. Scand J Immunol Suppl 5:9–15CrossRefGoogle Scholar
  8. 8.
    Boyum A (1984) Separation of lymphocytes, granulocytes, and monocytes from human blood using iodinated density gradient media. Methods Enzymol 108:88–102PubMedCrossRefGoogle Scholar
  9. 9.
    Cantey JR, Hand WL (1974) Cell-mediated immunity after bacterial infection of the lower respiratory tract. J Clin Invest 54:1125–1134PubMedCrossRefGoogle Scholar
  10. 10.
    Hand WL, King-Thompson NL (1982) Membrane transport of clindamycin in alveolar macrophages. Antimicrob Agents Chemother 21:241–247PubMedGoogle Scholar
  11. 11.
    Steinberg TH, Hand WL (1984) Effects of phagocytosis on antibiotic and nuceloside uptake by human polymorphonuclear leukocytes. J Infect Dis 149:397–403PubMedCrossRefGoogle Scholar
  12. 12.
    Hand WL, King-Thompson NL, Holman JW (1987) Entry of roxithromycin (RU 965), imipenem, cefotaxime, trimethoprim, and metronidazole into human polymorphonuclear leukocytes. Antimicrob Agents Chemother 31:1553–1557PubMedGoogle Scholar
  13. 13.
    Hand WL, King-Thompson NL (1986) Contrasts between phasocyte antibiotic uptake and subsequent intracellular bactericidal activity. Antimicrob Agents Chemother 29:135–140PubMedGoogle Scholar
  14. 14.
    Steinberg TH, Hand WL (1987) Effect of phagocyte membrane stimulation on antibiotic uptake and intracellular bactericidal activity. Antimicrob Agents Chemother 31:660–662PubMedGoogle Scholar
  15. 15.
    Hand WL, King-Thompson NL, Johnson JD (1984) Influence of bacterial-antibiotic interactions on subsequent antimicrobial activity of alveolar macrophages. J Infect Dis 149:271–276PubMedCrossRefGoogle Scholar
  16. 16.
    Hand WL, Hand DL, King-Thompson NL Inhibition of oxidative metabolism in human polymorphonuclear leukocytes by clindamycin and nucleosides, (manuscript submitted)Google Scholar
  17. 17.
    Hand WL, King-Thompson NL (1983) Effect of erythrocyte ingestion on macrophage antibacterial function. Infect Immun 40:917–923PubMedGoogle Scholar
  18. 18.
    Johnston RB Jr, Keele BB, Misra HP, Lehmeyer JE, Webb LS, Baehner RL, Rajagopalan KV (1975) The role of superoxide anion generation in phagocytic bactericidal activity. J Clin Invest 55:1357–1372PubMedCrossRefGoogle Scholar
  19. 19.
    Crapo JD, McCord JE, Fridovich I (1978) Preparation and assay of superoxide dismutase. Methods Enzymol 53:382–393PubMedCrossRefGoogle Scholar
  20. 20.
    Root RK, Metcalf J, Oshino N, Chance B (1975) H2O2 release from human granulocytes during phagocytosis. I. Documentation, quantitation, and some regulating factors. J Clin Invest 55:945–955PubMedCrossRefGoogle Scholar
  21. 21.
    Root RK, Metcalf JA (1977) H2O2 release from human granulocytes during phagocytosis. Relationship to superoxide anion formation and cellular catabolism of H2O2: studies with normal and cytochalasin β-treated cells. J Clin Invest 60:1266–1279PubMedCrossRefGoogle Scholar
  22. 22.
    Holmes B, Quie PG, Windhorst DB, Pollara B, Good RA (1966) Protection of phagocytized bacteria from the killing action of antibiotics. Nature 210:1131–1132PubMedCrossRefGoogle Scholar
  23. 23.
    Mandell GL, Vest TK (1973) Killing of intraleukocytic Staphylococcus aureus by rifampin: in-vitro and in-vivo studies. J Infect Dis 125:486–490CrossRefGoogle Scholar
  24. 24.
    Solberg CO (1972) Protection of phagocytized bacteria against antibiotics. Acta Med Scand 191:383–387PubMedGoogle Scholar
  25. 25.
    Vandaux P, Waldvogel FA (1979) Gentamicin antibacterial activity in the presence of human polymorphonuclear leukocytes. Antimicrob Agents Chemother 16:743–749Google Scholar
  26. 26.
    Jacobs RF, Wilson CB, Laxton JG, Haas JE, Smith AL (1982) Cellular uptake and intracellular activity of antibiotics against Haemophilus influenzae type b. J Infect Dis 145:152–159PubMedCrossRefGoogle Scholar
  27. 27.
    Easmon CSF, Crane JP (1984) Cellular uptake of clindamycin and lincomycin. Br J Exp Pathol 65:725–730PubMedGoogle Scholar
  28. 28.
    Cronstein BN, Kramer SB, Weissman G, Hirschhorn R (1983) Adenosine: a physiological modulator of superoxide anion generation by human neutrophils. J Exp Med 158:1160–1177PubMedCrossRefGoogle Scholar
  29. 29.
    Cronstein BN, Rosenstein ED, Kramer SB, Weissmann G, Hirschhorn R (1985) Adenosine: a physiologic modulator of superoxide anion generation by human neutrophils. Adenosine acts via an A2 receptor on human neutrophils. J Immunol 135:1366–1371PubMedGoogle Scholar
  30. 30.
    Castagna M, Takai Y, Kaibuchi K, Sano K, Kikkawa U, Nishizuka Y (1982) Direct activation of calcium-activated phospholipid-dependent protein kinase by tumor-promoting phorbol esters. J Biol Chem 257:7847–7851PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • W. L. Hand
  • N. L. King-Thompson
  • T. H. Steinberg
  • D. L. Hand

There are no affiliations available

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