Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1989 Dec;84(6):2017–2020. doi: 10.1172/JCI114394

Monocyte-chemotactic activity of defensins from human neutrophils.

M C Territo 1, T Ganz 1, M E Selsted 1, R Lehrer 1
PMCID: PMC304087  PMID: 2592571

Abstract

We investigated the monocyte-chemotactic activity of fractionated extracts of human neutrophil granules. Monocyte-chemotactic activity was found predominantly in the defensin-containing fraction of the neutrophil granules. Purified preparations of each of the three human defensins (HNP-1, HNP-2, HNP-3) were then tested. HNP-1 demonstrated significant chemotactic activity for monocytes: Peak activity was seen at HNP-1 concentrations of 5 X 10(-9) M and was 49 +/- 20% (mean +/- SE, n = 9) of that elicited by 10(-8) M FMLP. HNP-2 (peak activity at 5 X 10(-9) M) was somewhat less active, yielding 19 +/- 10% (n = 11). HNP-3 failed to demonstrate chemotactic activity. Checkerboard analysis of monocyte response to HNP-1 and HNP-2 confirmed that their activity was chemotactic rather than chemokinetic. Neutrophils demonstrated a low level of response to defensins but this reaction was primarily chemokinetic. Defensins may play a role in the recruitment of monocytes by neutrophils into inflammatory sites.

Full text

PDF
2017

Selected References

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

  1. Baggiolini M., Dewald B. Exocytosis by neutrophils. Contemp Top Immunobiol. 1984;14:221–246. doi: 10.1007/978-1-4757-4862-8_8. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Clark R. A., Wikner N. E., Doherty D. E., Norris D. A. Cryptic chemotactic activity of fibronectin for human monocytes resides in the 120-kDa fibroblastic cell-binding fragment. J Biol Chem. 1988 Aug 25;263(24):12115–12123. [PubMed] [Google Scholar]
  4. Dale D. C., Wolff S. M. Skin window studies of the acute inflammatory responses of neutropenic patients. Blood. 1971 Aug;38(2):138–142. [PubMed] [Google Scholar]
  5. Doherty D. E., Downey G. P., Worthen G. S., Haslett C., Henson P. M. Monocyte retention and migration in pulmonary inflammation. Requirement for neutrophils. Lab Invest. 1988 Aug;59(2):200–213. [PubMed] [Google Scholar]
  6. Falk W., Goodwin R. H., Jr, Leonard E. J. A 48-well micro chemotaxis assembly for rapid and accurate measurement of leukocyte migration. J Immunol Methods. 1980;33(3):239–247. doi: 10.1016/0022-1759(80)90211-2. [DOI] [PubMed] [Google Scholar]
  7. Gallin J. I., Fletcher M. P., Seligmann B. E., Hoffstein S., Cehrs K., Mounessa N. Human neutrophil-specific granule deficiency: a model to assess the role of neutrophil-specific granules in the evolution of the inflammatory response. Blood. 1982 Jun;59(6):1317–1329. [PubMed] [Google Scholar]
  8. Ganz T. Extracellular release of antimicrobial defensins by human polymorphonuclear leukocytes. Infect Immun. 1987 Mar;55(3):568–571. doi: 10.1128/iai.55.3.568-571.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ganz T., Metcalf J. A., Gallin J. I., Boxer L. A., Lehrer R. I. Microbicidal/cytotoxic proteins of neutrophils are deficient in two disorders: Chediak-Higashi syndrome and "specific" granule deficiency. J Clin Invest. 1988 Aug;82(2):552–556. doi: 10.1172/JCI113631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Ganz T., Selsted M. E., Szklarek D., Harwig S. S., Daher K., Bainton D. F., Lehrer R. I. Defensins. Natural peptide antibiotics of human neutrophils. J Clin Invest. 1985 Oct;76(4):1427–1435. doi: 10.1172/JCI112120. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Goldstein I. M. Neutrophil degranulation. Contemp Top Immunobiol. 1984;14:189–219. doi: 10.1007/978-1-4757-4862-8_7. [DOI] [PubMed] [Google Scholar]
  12. Greenwald G. I., Ganz T. Defensins mediate the microbicidal activity of human neutrophil granule extract against Acinetobacter calcoaceticus. Infect Immun. 1987 Jun;55(6):1365–1368. doi: 10.1128/iai.55.6.1365-1368.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Humphrey D. M., McManus L. M., Hanahan D. J., Pinckard R. N. Morphologic basis of increased vascular permeability induced by acetyl glyceryl ether phosphorylcholine. Lab Invest. 1984 Jan;50(1):16–25. [PubMed] [Google Scholar]
  14. Lehrer R. I., Ganz T., Selsted M. E., Babior B. M., Curnutte J. T. Neutrophils and host defense. Ann Intern Med. 1988 Jul 15;109(2):127–142. doi: 10.7326/0003-4819-109-2-127. [DOI] [PubMed] [Google Scholar]
  15. Lewis R. A., Austen K. F. The biologically active leukotrienes. Biosynthesis, metabolism, receptors, functions, and pharmacology. J Clin Invest. 1984 Apr;73(4):889–897. doi: 10.1172/JCI111312. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Malech H. L., Gallin J. I. Current concepts: immunology. Neutrophils in human diseases. N Engl J Med. 1987 Sep 10;317(11):687–694. doi: 10.1056/NEJM198709103171107. [DOI] [PubMed] [Google Scholar]
  17. Modrzakowski M. C., Cooney M. H., Martin L. E., Spitznagel J. K. Bactericidal activity of fractionated granule contents from human polymorphonuclear leukocytes. Infect Immun. 1979 Mar;23(3):587–591. doi: 10.1128/iai.23.3.587-591.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Rice W. G., Ganz T., Kinkade J. M., Jr, Selsted M. E., Lehrer R. I., Parmley R. T. Defensin-rich dense granules of human neutrophils. Blood. 1987 Sep;70(3):757–765. [PubMed] [Google Scholar]
  19. Ward P. A. Chemotoxis of mononuclear cells. J Exp Med. 1968 Nov 1;128(5):1201–1221. doi: 10.1084/jem.128.5.1201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Wright D. G., Gallin J. I. A functional differentiation of human neutrophil granules: generation of C5a by a specific (secondary) granule product and inactivation of C5a by azurophil (primary) granule products. J Immunol. 1977 Sep;119(3):1068–1076. [PubMed] [Google Scholar]
  21. Zigmond S. H., Hirsch J. G. Leukocyte locomotion and chemotaxis. New methods for evaluation, and demonstration of a cell-derived chemotactic factor. J Exp Med. 1973 Feb 1;137(2):387–410. doi: 10.1084/jem.137.2.387. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES