Abstract
Defensins are known to be the microbicidal components of neutrophil granules, which contribute to oxygen-independent antimicrobial mechanisms. In this study, we have examined the effect of defensins on neutrophil functions, such as adhesion, superoxide anion generation, phagocytosis and chemotaxis. Guinea-pig defensins increased the expression of CD11b, CD11c and CD54 (intercellular adhesion molecule ICAM-1) on human neutrophils, and induced adhesion of guinea-pig and human neutrophils. When the effect of guinea-pig defensins on superoxide anion generation was examined, defensins inhibited superoxide anion generation during phagocytosis of complement-opsonized particles. Furthermore, defensins inhibited complement-dependent phagocytosis. However, they did not inhibit the binding of complement-opsonized particles to neutrophils, suggesting that defensins possibly inhibit complement-dependent phagocytosis by affecting the ingestion step but not the binding step. Defensins exhibited neither chemotactic nor chemokine activity. Interestingly, 10–20% of total defensins were released extracellularly from phagocytosing neutrophils. Together these observations indicate that, in addition to their antimicrobial activity, defensins may have the ability to modulate the functions of neutrophils at sites of infection or inflammation.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Lehrer RI, Ganz T, Selsted ME, Babior BM, Curnutte JT. Neutrophils and host defense. Ann Intern Med 1988;109:127–42.
Klebanoff SJ. Oxygen metabolites from phagocytes. In: Gallin JI, Goldstein IM, Snyderman R, editors. Inflammation: Basic Principles and Clinical Correlates. 2nd ed. New York: Raven Press, 1992:541–601.
Elsbach P, Weiss J, Oxygen-independent antimicrobial systems of phagocytes. In Gallin JI, Goldstein IM, Snyderman R, editors. Inflammation: Basic Principles and Clinical Correlates. 2nd ed. New York: Raven Press, 1992:603–36.
Spitznagel JK. Antibiotic proteins of human neutrophils. J Clin Invest 1990;86:1381–6.
Lehrer RI, Ganz T.. Antimicrobial polypeptides of human neutrophils. Blood 1990;76:2169–81.
Ganz T, Selsted ME, Lehrer RI. Defensins. Eur J Haematol 1990;44:1–8.
Lehrer RI, Lichtenstein AK, Ganz T.. Defensins: antimicrobial and cytotoxic peptides of mammalian cells. Ann Rev Immunol 1993;11:105–28.
Yamashita T, Saito K. Purification, primary structure, and biological activity of guinea pig neutrophil cationic peptides. Infect Immun 1989;57:2405–9.
Territo MC, Ganz T, Selsted ME, Lehrer RI. Monocytechemotactic activity of defensins from human neutrophils. J Clin Invest 1989;84:2017–20.
Nagaoka I, Yamashita T. Comparative studies on the leucine aminopeptidase activity of different types of leukocytes. Comp Biochem Physiol 1984;79B:147–51.
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein Measurement with the folin phenol reagent. J Biol Chem 1951; 193:265–75.
Iwabuchi K, Yamashita T. Localization of neutrophil adherence-inhibiting factor in guinea pig platelets. Biochim Biophys Acta 1987;931:294–302.
Keizer GD, Borst J, Visser W, Schwarting R, de Vries JE, Figdor CG. Membrane glycoprotein p150,95 of human cytotoxic T cell clones is involved in conjugate formation with target cells. J Immunol 1987;138:3130–6.
Ishibashi Y, Yamashita T: Effect of a phagocytosis-stimulating factor on the phagocytic process of polymorphonuclear neutrophils. Infect Immun 1982;38:825–33.
Yamashita T, Someya A, Tsuzawa-Kido Y. Effect of maleimide derivatives on superoxide-generating system of guinea-pig neutrophils stimulated by different soluble stimuli. Eur J Biochem 1984;145:71–6.
Johnston RB Jr., Godzik CA, Cohn ZA. Increased superoxide anion production by immunologically activated and chemically elicited macrophage. J Exp Med 1978;148:115–27.
Nagaoka I, Yamashita T. Inactivation during phagocytosis of leucine aminopeptidase, an ecto-enzyme of polymorphonuclear neutrophils. Biochim Biophys Acta 1981;678:342–51.
Nagaoka I, Yomogida S, Nakamura S, Someya A, Iwabuchi K, Yamashita T. Evaluation of the expression of the cationic peptide gene in various types of leukocytes. FEBS Lett 1992;164:279–283.
Nagaoka I, Yamashita T. Possible involvement of aminopeptidase, an ecto-enzyme, in the inactivation of bradykinin by intact neutrophils. Biochim Biophys Acta 1985;847:67–76.
Albelda SM, Smith CW, Ward PA. Adhesion molecules and inflammatory injury. FASEB J 1994;8:504–12.
Timothy MC, Harlan MJ. Leukocyte-endothelial adhesion molecules. Blood 1994;84:2068–101.
Rosales C, Juliano RL. Signal transduction by cell adhesion receptors in leukocytes. J Leukoc Biol 1995;57:189–98.
Nathan C, Sanchez E. Tumor necrosis factor and CD11/CD18 (β2) integrins act synergistically to lower cAMP in human neutrophils. J Cell Biol 1990;111:2171–81.
Yamashita T. Selective inhibition by the sulfhydryl reagent maleimide of zymosan particle phagocytosis by neutrophils. FEBS Lett 1982;141:68–73.
Author information
Authors and Affiliations
Additional information
accepted by M. J. Parnham
Rights and permissions
About this article
Cite this article
Yomogida, S., Nagaoka, I., Saito, K. et al. Evaluation of the effects of defensins on neutrophil functions. Inflamm Res 45, 62–67 (1996). https://doi.org/10.1007/BF02265117
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02265117