Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1986 Jun;52(3):748–755. doi: 10.1128/iai.52.3.748-755.1986

Differential contribution of chemotaxins and opsonins to neutrophil-mediated killing of Schistosoma mansoni larvae.

C H King, P J Spagnuolo, J J Ellner
PMCID: PMC260922  PMID: 3011674

Abstract

In neutrophil-mediated killing of schistosomula, antibody and serum complement serve two functions: (i) opsonization of the target pathogen and (ii) generation of cell-activating, chemotactic peptides. We studied neutrophil-mediated schistosomulum killing in experiments designed to isolate these functions of antibody and complement in the cell activation response of neutrophils to external pathogens. Schistosomula opsonized by antibody or antibody plus complement induced neutrophil-mediated killing, while complement-opsonized larvae did not. Antibody enhancement of cell-mediated killing correlated with increased cell-to-parasite adherence, while cell-mediated killing in the presence of fresh normal human serum (providing chemotactic factor stimulation and complement opsonization of larvae) demonstrated a dissociation between neutrophil adhesive and killing responses. Exogenous chemotactic stimuli were found to enhance significantly neutrophil-mediated killing of both opsonized and unopsonized larvae. Experiments involving parabiotic chambers confirmed that chemotactic-factor-stimulated neutrophils may cause significant parasite mortality without direct cell-parasite contact. In further analysis of the neutrophil response to surface and fluid-phase stimulation, release of neutrophil cytotoxic mediators was found to vary according to the type of stimulus provided: cell exposure to either larvae opsonized by antibody plus complement or to chemotactic factors provoked low-to-moderate cell release of superoxide anion, granule enzymes, and arginase; when opsonic and chemotactic stimuli were combined, a greater-than-additive secretory response was noted. Under such maximal stimulation, oxidative and nonoxidative mediators were synergistic in effecting neutrophil-mediated parasite killing. The primary function of complement in cell-mediated parasite killing appears to be to promote chemotactic-factor-mediated cellular release of toxic agents and not cell-target linkage, whereas antibody-mediated adherence is associated with concurrent cellular activation. Both neutrophils adherent to the antibody-opsonized schistosomulum and chemotactic-factor-stimulated cells (adherent and not adherent to the parasite) appear to contribute significantly to its demise.

Full text

PDF
748

Selected References

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

  1. Anwar A. R., McKean J. R., Smithers S. R., Kay A. B. Human eosinophil- and neutrophil-mediated killing of schistosomula of Schistosoma mansoni in vitro. I. Enhancement of complement-dependent damage by mast cell-derived mediators and formyl methionyl peptides. J Immunol. 1980 Mar;124(3):1122–1129. [PubMed] [Google Scholar]
  2. Bass D. A., Dechatelet L. R., McCall C. E. Independent stimulation of motility and the oxidative metabolic burst of human polymorphonuclear leukocytes. J Immunol. 1978 Jul;121(1):172–178. [PubMed] [Google Scholar]
  3. Butterworth A. E., Wassom D. L., Gleich G. J., Loegering D. A., David J. R. Damage to schistosomula of Schistosoma mansoni induced directly by eosinophil major basic protein. J Immunol. 1979 Jan;122(1):221–229. [PubMed] [Google Scholar]
  4. Böyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl. 1968;97:77–89. [PubMed] [Google Scholar]
  5. Caulfield J. P., Korman G., Butterworth A. E., Hogan M., David J. R. The adherence of human neutrophils and eosinophils to schistosomula: evidence for membrane fusion between cells and parasites. J Cell Biol. 1980 Jul;86(1):46–63. doi: 10.1083/jcb.86.1.46. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Clark R. A., Olsson I., Klebanoff S. J. Cytotoxicity for tumor cells of cationic proteins from human neutrophil granules. J Cell Biol. 1976 Sep;70(3):719–723. doi: 10.1083/jcb.70.3.719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Clegg J. A., Smithers S. R. The effects of immune rhesus monkey serum on schistosomula of Schistosoma mansoni during cultivation in vitro. Int J Parasitol. 1972 Mar;2(1):79–98. doi: 10.1016/0020-7519(72)90036-7. [DOI] [PubMed] [Google Scholar]
  8. Ellner J. J., Mahmoud A. A. Phagocytes and worms: David and Goliath revisited. Rev Infect Dis. 1982 May-Jun;4(3):698–714. doi: 10.1093/clinids/4.3.698. [DOI] [PubMed] [Google Scholar]
  9. Fehr J., Dahinden C. Modulating influence of chemotactic factor-induced cell adhesiveness on granulocyte function. J Clin Invest. 1979 Jul;64(1):8–16. doi: 10.1172/JCI109466. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gallin J. I., Clark R. A., Kimball H. R. Granulocyte chemotaxis: an improved in vitro assay employing 51 Cr-labeled granulocytes. J Immunol. 1973 Jan;110(1):233–240. [PubMed] [Google Scholar]
  11. Gallin J. I., Wright D. G., Schiffmann E. Role of secretory events in modulating human neutrophil chemotaxis. J Clin Invest. 1978 Dec;62(6):1364–1374. doi: 10.1172/JCI109257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Goldstein I. M., Kaplan H. B., Radin A., Frosch M. Independent effects of IgG and complement upon human polymorphonuclear leukocyte function. J Immunol. 1976 Oct;117(4):1282–1287. [PubMed] [Google Scholar]
  13. Goldstein I. M., Roos D., Kaplan H. B., Weissmann G. Complement and immunoglobulins stimulate superoxide production by human leukocytes independently of phagocytosis. J Clin Invest. 1975 Nov;56(5):1155–1163. doi: 10.1172/JCI108191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Goldstein I., Hoffstein S., Gallin J., Weissmann G. Mechanisms of lysosomal enzyme release from human leukocytes: microtubule assembly and membrane fusion induced by a component of complement. Proc Natl Acad Sci U S A. 1973 Oct;70(10):2916–2920. doi: 10.1073/pnas.70.10.2916. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hafeman D. G., Lewis J. T., McConnell H. M. Triggering of the macrophage and neutrophil respiratory burst by antibody bound to a spin-label phospholipid hapten in model lipid bilayer membranes. Biochemistry. 1980 Nov 11;19(23):5387–5394. doi: 10.1021/bi00564a037. [DOI] [PubMed] [Google Scholar]
  16. Horwitz M. A., Silverstein S. C. Influence of the Escherichia coli capsule on complement fixation and on phagocytosis and killing by human phagocytes. J Clin Invest. 1980 Jan;65(1):82–94. doi: 10.1172/JCI109663. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Incani R. N., McLaren D. J. Neutrophil-mediated cytotoxicity to schistosomula of Schistosoma mansoni in vitro: studies on the kinetics of complement and/or antibody-dependent adherence and killing. Parasite Immunol. 1981 Summer;3(2):107–126. doi: 10.1111/j.1365-3024.1981.tb00389.x. [DOI] [PubMed] [Google Scholar]
  18. James S. L., Sher A. Immune mechanisms that stimulate mouse leukocyte migration in response to schistosomula of Schistosoma mansoni. J Immunol. 1980 Apr;124(4):1837–1844. [PubMed] [Google Scholar]
  19. Jong E. C., Chi E. Y., Klebanoff S. J. Human neutrophil-mediated killing of schistosomula of Schistosoma mansoni: augmentation by schistosomal binding of eosinophil peroxidase. Am J Trop Med Hyg. 1984 Jan;33(1):104–115. doi: 10.4269/ajtmh.1984.33.104. [DOI] [PubMed] [Google Scholar]
  20. Kazura J. W., Fanning M. M., Blumer J. L., Mahmoud A. A. Role of cell-generated hydrogen peroxide in granulocyte-mediated killing of schistosomula of Schistosoma mansoni in vitro. J Clin Invest. 1981 Jan;67(1):93–102. doi: 10.1172/JCI110037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. McKean J. R., Anwar A. R., Kay A. B. Schistosoma mansoni: complement and antibody damage, mediated by human eosinophils and neutrophils, in killing schistosomula in vitro. Exp Parasitol. 1981 Jun;51(3):307–317. doi: 10.1016/0014-4894(81)90118-1. [DOI] [PubMed] [Google Scholar]
  22. Moser G., Sher A. Studies of the antibody-dependent killing of schistosomula of Schistosoma mansoni employing haptenic target antigens. II. In vitro killing of TNP-schistosomula by human eosinophils and neutrophils. J Immunol. 1981 Mar;126(3):1025–1029. [PubMed] [Google Scholar]
  23. Moser G., Wassom D. L., Sher A. Studies of the antibody-dependent killing of schistosomula of Schistosoma mansoni employing haptenic target antigens. I. Evidence that the loss in susceptibility to immune damage undergone by developing schistosomula involves a change unrelated to the masking of parasite antigens by host molecules. J Exp Med. 1980 Jul 1;152(1):41–53. doi: 10.1084/jem.152.1.41. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Olds G. R., Ellner J. J., Kearse L. A., Jr, Kazura J. W., Mahmoud A. A. Role of arginase in killing of schistosomula of Schistosoma mansoni. J Exp Med. 1980 Jun 1;151(6):1557–1562. doi: 10.1084/jem.151.6.1557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Peck C. A., Carpenter M. D., Mahmoud A. A. Species-related innate resistance to Schistosoma mansoni. Role of mononuclear phagocytes in schistosomula killing in vitro. J Clin Invest. 1983 Jan;71(1):66–72. doi: 10.1172/JCI110752. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Root R. K., Metcalf J., Oshino N., Chance B. H2O2 release from human granulocytes during phagocytosis. I. Documentation, quantitation, and some regulating factors. J Clin Invest. 1975 May;55(5):945–955. doi: 10.1172/JCI108024. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rosen H., Klebanoff S. J. Bactericidal activity of a superoxide anion-generating system. A model for the polymorphonuclear leukocyte. J Exp Med. 1979 Jan 1;149(1):27–39. doi: 10.1084/jem.149.1.27. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Rüegg U. T., Russell A. S. A rapid and sensitive assay for arginase. Anal Biochem. 1980 Feb;102(1):206–212. doi: 10.1016/0003-2697(80)90340-1. [DOI] [PubMed] [Google Scholar]
  29. SENFT A. W. OBSERVATIONS ON AMINO ACID METABOLISM OF SCHISTOSOMA MANSONI IN A CHEMICALLY DEFINED MEDIUM. Ann N Y Acad Sci. 1963 Dec 30;113:272–288. doi: 10.1111/j.1749-6632.1963.tb40670.x. [DOI] [PubMed] [Google Scholar]
  30. SMOLELIS A. N., HARTSELL S. E. The determination of lysozyme. J Bacteriol. 1949 Dec;58(6):731–736. doi: 10.1128/jb.58.6.731-736.1949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Samuelson J. C., Sher A., Caulfield J. P. Newly transformed schistosomula spontaneously lose surface antigens and C3 acceptor sites during culture. J Immunol. 1980 Apr;124(4):2055–2057. [PubMed] [Google Scholar]
  32. Santoro F., Lachmann P. J., Capron A., Capron M. Activation of complement by Schistosoma mansoni schistosomula: killing of parasites by the alternative pathway and requirement of IgG for classical pathway activation. J Immunol. 1979 Oct;123(4):1551–1557. [PubMed] [Google Scholar]
  33. Smith C. W., Hollers J. C., Patrick R. A., Hassett C. Motility and adhesiveness in human neutrophils. Effects of chemotactic factors. J Clin Invest. 1979 Feb;63(2):221–229. doi: 10.1172/JCI109293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. TENNANT J. R. EVALUATION OF THE TRYPAN BLUE TECHNIQUE FOR DETERMINATION OF CELL VIABILITY. Transplantation. 1964 Nov;2:685–694. doi: 10.1097/00007890-196411000-00001. [DOI] [PubMed] [Google Scholar]
  35. Terayama H., Koji T., Kontani M., Okumoto T. Arginase as an inhibitory principle in liver plasma membranes arresting the growth of various mammalian cells in vitro. Biochim Biophys Acta. 1982 Apr 29;720(2):188–192. doi: 10.1016/0167-4889(82)90011-8. [DOI] [PubMed] [Google Scholar]
  36. Vadas M. A., Butterworth A. E., Sherry B., Dessein A., Hogan M., Bout D., David J. R. Interactions between human eosinophils and schistosomula of Schistosoma mansoni. I. Stable and irreversible antibody-dependent adherence. J Immunol. 1980 Mar;124(3):1441–1448. [PubMed] [Google Scholar]
  37. Vadas M. A., David J. R., Butterworth A., Pisani N. T., Siongok T. A. A new method for the purification of human eosinophils and neutrophils, and a comparison of the ability of these cells to damage schistosomula of Schistosoma mansoni. J Immunol. 1979 Apr;122(4):1228–1236. [PubMed] [Google Scholar]
  38. Ward P. A., Newman L. J. A neutrophil chemotactic factor from human C'5. J Immunol. 1969 Jan;102(1):93–99. [PubMed] [Google Scholar]
  39. von Lichtenberg F., Byram J. E. Pulmonary cell reactions in natural and acquired host resistance to Schistosoma mansoni. Am J Trop Med Hyg. 1980 Nov;29(6):1286–1300. doi: 10.4269/ajtmh.1980.29.1286. [DOI] [PubMed] [Google Scholar]

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

RESOURCES