Structure and Properties of a Novel Neutrophil-Activating Factor (NAF) Produced by Human Monocytes

  • A. Walz
  • P. Peveri
  • H. Aschauer
  • B. Dewald
  • M. Baggiolini
Conference paper

Abstract

Neutrophils are the main cellular elements of antimicrobial defense and acute inflammation. Their activity depends largely on the release of cytotoxic, tissue-damaging, and cell-activating products. A variety of stimulatory molecules of different origin are known to condition neutrophil activity in inflamed tissues. Among the best-characterized ones are N-formyl-methionyl peptides (e.g., fMLP) related to bacterial products (Showell et al. 1976), C5a formed upon complement activation (Fernandez et al. 1978), and two lipids, platelet-activating factor (PAF) and leukotriene B4 (LTB4) (Dewald and Baggiolini 1986), which are released by stimulated phagocytes (Baggiolini et al. 1988). At sites of chronic inflammation, neutrophils are exposed to the products of activated mononuclear phagocytes which are prominent in such lesions. We have studied the production of neutrophil-activating factors by human monocytes stimulated in different ways, and describe here one of these factors, termed NAF, which binds to human neutrophils via a selective surface receptor and acts like the chemotactic agonists C5a and fMLP.

Keywords

Superoxide Serine Fluores Stim Cycloheximide 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Baggiolini M, Dewald B, Thelen M (1988) Effects of PAF on neutrophils and mononuclear phagocytes. Prog Biochem Pharmacol 22: 90PubMedGoogle Scholar
  2. Dewald B, Baggiolini M (1986) Platelet-activating factor as a stimulus of exocytosis in human neutrophils. Biochim Biophys Acta 888: 42PubMedCrossRefGoogle Scholar
  3. Fernandez HN, Henson PM, Otani A, Hugli TE (1978) Chemotactic response to human C3a and C5a anaphylatoxins. J Immunol 120: 109PubMedGoogle Scholar
  4. Hunninghake GW, Gadek JE, Fale HM, Crystal RG (1980) Human alveolar macrophage-derived chemotactic factor for neutrophils. J Clin Invest 66: 473PubMedCrossRefGoogle Scholar
  5. Kapp A, Luger TA, Maly FA, Schoepf F (1986) Granulocyte-activating mediators (GRAM): I. Generation by lipopolysaccharide-stimulated mononuclear cells. J Invest Dermatol 86: 523PubMedCrossRefGoogle Scholar
  6. Kazmierowski J A, Gallin JI, Reynolds HY (1977) Mechanism for the inflammatory response in primate lungs. J Clin Invest 59: 273PubMedCrossRefGoogle Scholar
  7. Kownatzki E, Kapp A, Uhrich S (1986) Novel neutrophil chemotactic factor derived from human peripheral blood mononuclear leukocytes. Clin Exp Immunol 64: 214PubMedGoogle Scholar
  8. Merrill WW, Naegel GP, Matthay RA, Reynolds HY (1980) Alveolar macrophage-derived chemotactic factor. J Clin Invest 65: 268PubMedCrossRefGoogle Scholar
  9. Pennington JE, Rossing TH, Boerth LW (1983) The effect of human alveolar macrophages on the bactericidal capacity of neutrophils. J Infect Dis 148: 101PubMedCrossRefGoogle Scholar
  10. Pennington JE, Rossing TH, Boerth LW, Lee TH (1985) Isolation and partial characterization of a human alveolar macrophage-derived neutrophil-activating factor. J Clin Invest 75: 1230PubMedCrossRefGoogle Scholar
  11. Peveri P, Walz A, Dewald B, Baggiolini M (1988) A novel neutrophil-activating factor produced by human mononuclear phagocytes. J Exp Med 167: 1547PubMedCrossRefGoogle Scholar
  12. Schmid J, Weissmann C (1987) Induction of mRNA for a serine protease and a beta-thromboglobulin-like protein in mitogen-stimulated human leukocytes. J Immunol 139: 250PubMedGoogle Scholar
  13. Schroeder JM, Mrowietz U, Morita E, Christophers E (1987) Purification and partial biochemical characterization of a human monocyte-derived, neutrophil-activating peptide that lacks interleukin 1 activity. J Immunol 139: 3474Google Scholar
  14. Showell HJ, Freer RJ, Zigmond SH, Schiffmann E, Aswanikumar S, Corcoran B, Becker EL (1976) The structure-activity relations of synthetic peptides as chemotactic factors and inducers of lysosomal enzyme secretion for neutrophils. J Exp Med 143: 1154PubMedCrossRefGoogle Scholar
  15. von Tscharner V, Prod’hom B, Baggiolini M, Reuter H (1986) Ion channels in human neutrophils activated by a rise in free cytosolic calcium concentration. Nature 324: 369CrossRefGoogle Scholar
  16. Walz A, Peveri P, Aschauer H, Baggiolini M (1987) Purification and amino acid sequencing of NAF, a novel neutrophil-activating factor produced by monocytes. Biochem Biophys Res Commun 149: 755PubMedCrossRefGoogle Scholar
  17. Wymann MP, von Tscharner V, Deranleau DA, Baggiolini M (1987) The onset of the respiratory burst in human neutrophils. J Biol Chem 262: 12048PubMedGoogle Scholar
  18. Yoshimura T, Matsushima K, Tanaka S, Robinson EA, Appella E, Oppenheim JJ, Leonard EJ (1987) Purification of a human monocyte-derived chemotactic factor that shares sequence homology with other host defense cytokines. Proc Natl Acad Sci USA 84: 9233PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag, Berlin Heidelberg 1989

Authors and Affiliations

  • A. Walz
  • P. Peveri
  • H. Aschauer
  • B. Dewald
  • M. Baggiolini

There are no affiliations available

Personalised recommendations