Human Neutrophil Granule Cationic Protein CAP37 is a Specific Macrophage Chemotaxin that Shares Homology with Inflammatory Proteinases

  • John G. Morgan
  • H. Anne Pereira
  • Teresa Sukiennicki
  • John K. Spitznagel
  • James W. Larrick
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 305)


Cationic antimicrobial protein CAP37 (Mr = 37 kD) is derived from the azurophilic granules of human PMN. In vitro and in vivo studies demonstrate that CAP37 is a novel monocyte-specific chemoattractant. The N-terminal amino acid sequence of CAP37 shares significant homology with a number of inflammatory molecules with protease activity including elastase and cathepsin G. However, substitutions in the catalytic triad (serine for a histidine at position 41 and glycine for a serine at position 175), may account for its lack of serine protease activity. A full length cDNA for CAP37 was identified in an HL60 cDNA library screened with oligonucleotide probes designed from the N-terminal amino acid sequence. Sequencing of the cDNA reveals a protein of 225 amino acids with significant nucleotide homology to cathepsin G and human neutrophil elastase.


Serine Protease Catalytic Triad Human Neutrophil Elastase Azurophil Granule Serine Protease Activity 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Wilkinson, P.C. 1982. Locomotion and Chemotaxis of individual leucocyte types. Chemotaxis and inflammation, 2nd Ed. Edinburgh: Churchill Livingstone, 119–135.Google Scholar
  2. 2.
    Ward, P.A. 1968. Chemotaxis of mononuclear cells. J. Exp. Med. 128: 1201–1210.PubMedCrossRefGoogle Scholar
  3. 3.
    Gallin, J.I. 1985. Neutrophil specific granule deficiency. Ann. Rev. Med. 36: 263–282.PubMedCrossRefGoogle Scholar
  4. 4.
    Page, A.R., R.A. Good. 1958. A clinical and experimental study of the function of neutrophils in the inflammatory response. Amer. J. Pathol. 34: 645–655.Google Scholar
  5. 5.
    Shafer, W.M., L.E. Martin, J.K. Spitznagel. 1986. Late intraphagosomal hydrogen ion concentration favours the in vitro antimicrobial capacity of a 37-kilodalton cationic granule protein of human neutrophil granules. Infect. Immun. 53: 651–655.PubMedGoogle Scholar
  6. 6.
    Modrzakowski, M.C., J.K. Spitznagel. 1979. Bactericidal activity of fractionated granule contents from human polymorphonuclear leucocytes: Antagonism of granule cationic proteins by lipopolysaccharide. Infect. Immun. 25: 597–602.PubMedGoogle Scholar
  7. 7.
    Pereira, H.C., W.M. Shafer, J. Pohl, L.E. Martin, J.K. Spitznagel. 1990. CAP37, a human neutrophil-derived chemotactic factor with monocyte specific activity. J. Clin. Invest. 85: 1468–1476.PubMedCrossRefGoogle Scholar
  8. 8.
    Leonard, E.J., T. Yoshimura. 1990. Human monocyte chemoattractant protein-1 (MCP-1). Immunology Today. 11: 97–100.PubMedCrossRefGoogle Scholar
  9. 9.
    Pereira, H.C., J.K. Spitznagel, J. Pohl, D. Wilson, W.M. Shafer, J. Morgan, I. Palings, J.W. Larrick. 1990. The 37 KD human neutrophil cationic protein shares homology with inflammatory proteinases. Life Sciences. 46: 189–196.PubMedCrossRefGoogle Scholar
  10. 10.
    Gabay, J.E., R.W. Scott, D. Campanelli, J. Griffith, C. Wilde, M.N. Marra, M. Seeger, C.F. Nathan. 1989. Antibiotic proteins of human polymorphonuclear leukocytes. Proc. Natl. Acad. Sci. USA. 86: 5610–5614.PubMedCrossRefGoogle Scholar
  11. 11.
    Salvesen, G., D. Farley, J. Shuman, A. Przybyla, C. Reily, J. Travis. 1987. Molecular cloning of human cathepsin G. Structural similarity to mast cell and cytotoxic lymphocyte proteinases. Bio. Chem. 26: 2289–2295.Google Scholar
  12. 12.
    Sinha, W., W. Watorek, S. Karr, J. Giles, W. Bode, J. Travis. 1987. Primary structure of human neutrophil elastase. Proc. Natl. Acad. Sci. 84: 2228–2223.PubMedCrossRefGoogle Scholar
  13. 13.
    Okano, K., Y. Aoki, Sakurai, M. Kajitani, S. Kanai, T. Shimazu, H. Shimizu, M. Nruto. 1987. Molecular cloning of complementary DNA for human medullaisn; an inflammatory serine protease in bone marrow cells. J. Biol. Chem. 102: 13–19.Google Scholar
  14. 14.
    Farley, D., G. Salvensen, J. Travis. 1988. Molecular cloning of human neutrophil elastase. Bio. Chem. Hoppe. Seyler. 369: 3–11. (suppl.).Google Scholar
  15. 15.
    Keiser, H., R.A. Greenwald, G. Feinstein, A. Janoff. 1976. Degradation of cartilage proteoglycan by human leukocyte neutral proteases. A model of joint injury. II. Degradation of isolated bovine nasal cartilage proteoglycan. J.Clin.Invest. 57: 625–632.PubMedCrossRefGoogle Scholar
  16. 16.
    Barrett, A.J. 1981. Leukocyte elastase. Methods Enzymol. 80: 581–610.PubMedCrossRefGoogle Scholar
  17. 17.
    Cambell, E.J., R.M. Senior, J.A. McDonald, D.L. Cox. 1982. Proteolysis by neutrophils. Relative importance of cell-substrate contact and oxidative inactivation of proteinase inhibitors in vitro. J. Clin. Invest. 70: 845–852.CrossRefGoogle Scholar
  18. 18.
    Pipoly, D.J., E.C. Crouch. 1987. Degradation of native type IV procollagen by human neutrophil elastase. Implications for leucocyte-mediated degradation of basement membranes. Biochem. 26: 5748–5755.CrossRefGoogle Scholar
  19. 19.
    Baici, A., P. Salgam, K. Fehr, A. Boni. 1981. Inhibition of human elastase from polymorphonuclear leucocytes by gold sodium thiomalate and pentosan polysulfate. Biochem. Pharmacol. 30: 703–710.PubMedCrossRefGoogle Scholar
  20. 20.
    Starkey, P.M., A.J. Barrett, M.C. Burleigh. 1977. The degradation of articular collagen by neutrophil proteinases. Biochim. Biophys. Acta. 483: 386–392.PubMedGoogle Scholar
  21. 21.
    Ohlsson, K., L. Ohlsson. 1974. Neutral proteases of human granulocytes. III. Interaction between granulocyte elastase and plasma protease inhibitors. Scand. J. Clin. Lab. Invest. 34: 349–357.PubMedCrossRefGoogle Scholar
  22. 22.
    Barrett, A.J., P.M. Starkey. 1973. The interaction of alpha-2 macroglobulin with proteinases. Characteristics and specificity of the reaction and a hypothesis concerning its molecular mechanism. Biochem. J. 133: 709–715.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • John G. Morgan
    • 1
  • H. Anne Pereira
    • 2
  • Teresa Sukiennicki
    • 1
  • John K. Spitznagel
    • 2
  • James W. Larrick
    • 1
  1. 1.Genelabs Inc.Redwood CityUSA
  2. 2.Dept. of Microbiology and ImmunologyEmory University School of MedicineAtlantaUSA

Personalised recommendations