Identification and Characterization of Protein Tyrosine Phosphatases Expressed in Human Neutrophils

  • J. Kruger
  • T. Fukushima
  • G. P. Downey
Conference paper


The neutrophil is an important component of the innate immune system responsible for host defense. In this regard, it has a dual function: to destroy pathogenic microorganisms and to remove inflammatory debris. This functional role is achieved through a series of rapid and coordinated responses that include chemotaxis, phagocytosis, and intracellular killing of invading microorganisms. The latter is accomplished by release of a variety of microbicidal enzymes and cationic proteins contained in granules (exocytosis) and by production of reactive oxygen intermediates by the NADPH oxidase [1, 2]. In certain situations however, these toxic compounds can injure host tissues as is believed to occur in disorders characterized by inflammatory damage such as rheumatoid arthritis [3], inflammatory bowel disease [4, 5], and acute lung injury [6–8]. Thus to maintain homeostasis and minimize tissue damage, leukocyte microbicidal responses must be precisely regulated by processes including selective triggering and rapid termination of activation cascades once the initial stimulus has been removed. Currently the mechanisms which regulate neutrophil activation are incompletely understood.


Reverse Transcription Polymerase Chain Reaction Tyrosine Phosphorylation Human Neutrophil Malachite Green Protein Tyrosine Phosphatase 
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.
    Babior BM (1978) Oxygen-dependent microbial killing by phagocytosis. N Engl J Med 298: 659–668PubMedCrossRefGoogle Scholar
  2. 2.
    Badwey JA, Curnutte JT, Karnovsky ML (1979) The enzyme of granulocytes that produces Superoxide and peroxide. An elusive pimpernel. N Engl J Med 300: 1157–1160PubMedCrossRefGoogle Scholar
  3. 3.
    Weissmann G, Korchak H (1984) Rheumatoid arthritis. The role of neutrophil activation. Inflammation 8[Suppl]: S3–14PubMedCrossRefGoogle Scholar
  4. 4.
    Chester JF, Ross JS, Malt RA, Weitzman SA (1985) Acute colitis produced by chemotactic peptides in rats and mice. Am J Pathology 121: 284–290Google Scholar
  5. 5.
    Wandall JH (1985) Function of exudative neutrophilic granulocytes in patients with Crohn’s disease of ulceritive colitis. Scandinavian Journal of Gastroenterology 20: 1151–1156PubMedCrossRefGoogle Scholar
  6. 6.
    Stevens JH, Raffin TA (1984) Adult respiratory distress syndrome-I. Aetiology and mechanisms. Postgrad Med J 60: 505–513PubMedCrossRefGoogle Scholar
  7. 7.
    Weiland JE, Davis WB, Holter JF et al (1986) Lung neutrophils in the adult respiratory distress syndrome: Clinical and pathophysiologic significance. Am Rev Respir Dis 133: 218–225PubMedGoogle Scholar
  8. 8.
    Repine JE, Beehler CJ (1991) Neutrophils and adult respiratory distress syndrome: Two interlocking perspectives in 1991. Amer Rev Resp Dis 144: 251–252PubMedCrossRefGoogle Scholar
  9. 9.
    Babior BM (1988) Protein phosphorylation and the respiratory burst. Arch Biochem Biophys 264: 361–367PubMedCrossRefGoogle Scholar
  10. 10.
    Dusi S, Donini M, Delia Bianca V, Rossi F (1994) Tyrosine phosphorylation of phospholipase C-gamma 2 is involved in the activation of phosphoinositide hydrolysis by Fc receptors in human neutrophils. Biochem Biophys Res Commun 201: 1100–1108PubMedCrossRefGoogle Scholar
  11. 11.
    Greenberg S, Chang P, Silverstein SC (1993) Tyrosine phosphorylation is required for Fc receptor-mediated phagocytosis in mouse macrophages. J Exp Med 177: 529–534PubMedCrossRefGoogle Scholar
  12. 12.
    Berkow RL, Dodson RW, Kraft AS (1989) Human neutrophils contain distinct cytosolic and particulate tyrosine kinase activities: Possible role in neutrophil activation. Biochim Biophys Acta 997: 292–301PubMedCrossRefGoogle Scholar
  13. 13.
    Kusunoki T, Higashi H, Hosoi S et al (1992) Tyrosine phosphorylation and its possible role in Superoxide production by human neutrophils stimulated with FMLP and IgG. Biochem Biophys Res Commun 183: 789–796PubMedCrossRefGoogle Scholar
  14. 14.
    Huang CK, Laramee GR, Casnellie JE (1988) Chemotactic factor induced tyrosine phosphorylation of membrane associated proteins in rabbit peritoneal neutrophils. Biochem Biophys Res Commun 151: 794–801PubMedCrossRefGoogle Scholar
  15. 15.
    Gomez-Cambronero J, Huang CK, Bonak VA et al (1989) Tyrosine phosphorylation in human neutrophil. Biochem Biophys Res Commun 162: 1478–1485PubMedCrossRefGoogle Scholar
  16. 16.
    McGregor PE, Agrawal DK, Edwards JD (1994) Attenuation of human leukocyte adherence to endothelial cell monolayers by tyrosine kinase inhibitors. Biochem Biophys Res Commun 198: 359–365PubMedCrossRefGoogle Scholar
  17. 17.
    Gaudry M, Caon AC, Gilbert C et al (1992) Evidence for the involvement of tyrosine kinases in the locomotory responses of human neutrophils. J Leukoc Biol 51: 103–108PubMedGoogle Scholar
  18. 18.
    Kobayashi K, Takahashi K, Nagasawa S (1995) The role of tyrosine phosphorylation and Ca2+ accumulation in Fc gamma-receptor-mediated phagocytosis of human neutrophils. J Biochem (Tokyo) 117: 1156–1161Google Scholar
  19. 19.
    Grinstein S, Furuya W (1991) Tyrosine phosphorylation and oxygen consumption induced by G proteins in neutrophils. Am J Physiol 260: C1019–1027PubMedGoogle Scholar
  20. 20.
    LeBoeuf RD, Galin FS, Hollinger SK et al (1989) Cloning and sequencing of immunoglobulin variable-region genes using degenerate oligodeoxyribonucleotides and polymerase chain reaction. Gene 82: 371–377PubMedCrossRefGoogle Scholar
  21. 21.
    Yang Q, Tonks NK (1991) Isolation of a cDNA clone encoding a human protein-tyrosine phosphatase with homology to the cytoskeletal-associated proteins band 4.1, ezrin, and talin. PNAS 88: 5949–5953CrossRefGoogle Scholar
  22. 22.
    Rotin D, Goldstein BJ, Fladd CA (1994) Expression of the tyrosine phosphatase LAR-PTP2 is developmentally regulated in lung epithelia. Am J Physiol 267(3.1): L263–270PubMedGoogle Scholar
  23. 23.
    Haslett C, Guthne LA, Kopamak MM et al (1985) Modulation of multiple neutrophil functions by preparative methods or trace concentrations of bacterial lipopolysaccharide. Am J Pathol 119: 101–110PubMedGoogle Scholar
  24. 24.
    Chirgwin JM, Przybyla AE, MacDonald RJ, Rutter WJ (1979) Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochem 18: 5294–5299CrossRefGoogle Scholar
  25. 25.
    Groppe JC, Morse DE (1993) Isolation of full-length RNA templates for reverse transcription from tissues rich in RNase and proteoglycans. Analyt Biochem 210: 337–343PubMedCrossRefGoogle Scholar
  26. 26.
    Fialkow L, Chan CK, Rotin D et al (1994) Activation of the mitogen-activated protein kinase signaling pathway in neutrophils. Role of oxidants. J Biol Chem 269: 31234–31242PubMedGoogle Scholar
  27. 27.
    Lacal P, Pulido R, Sanchez-Madrid F, Mollinedo F (1988) Intracellular location of T200 and Mol glycoproteins in human neutrophils. The Journal of Biological Chemistry 263: 9946–9951PubMedGoogle Scholar
  28. 28.
    Pulido R, Lacal P, Mollinedo F, Sanchez-Madrid F (1989) Biochemical and antigenic characterization of CD45 polypeptides expressed on plasma membrane and integral granules of human neutrophils. FEBS Letters 249: 337–342PubMedCrossRefGoogle Scholar
  29. 29.
    Harvath L, Balke JA, Christiansen NP et al (1991) Selected antibodies to leukocyte common antigen (CD45) inhibit human neutrophil chemotaxis. J Immunol 146: 949–957PubMedGoogle Scholar
  30. 30.
    Fialkow L, Chan CK, Downey GP (1997) Regulation of CD45 in neutrophils: Modulation by oxidants. J Immunol 158: 5409–5417PubMedGoogle Scholar
  31. 31.
    Brumell JH, Chan CK, Butler J et al (1997) Regulation of Src homology 2-containing tyrosine phosphatase 1 during activation of human neutrophils. Role of protein kinase C J Biol Chem 272: 875–882Google Scholar
  32. 32.
    Frangioni JV, Beahm PH, Shifrin V et al (1992) The nontransmembrane tyrosine phosphatase PTP-1B localizes to the endoplasmic reticulum via its 35 amino acid C-terminal sequence. Cell 68: 545–560PubMedCrossRefGoogle Scholar
  33. 33.
    Hannig G, Ottilie S, Schievella AR, Erikson RL (1993) Comparison of the biochemical and biological functions of tyrosine phosphatases from fission yeast, budding yeast and animal cells. Yeast 9: 1039–1052PubMedCrossRefGoogle Scholar
  34. 34.
    Mishra S, Hamburger AW (1993) A microtiter enzyme-linked immunosorbent assay for protein tyrsoine phosphatase. Biochimica et Biophysica Acta 1157: 93–101PubMedCrossRefGoogle Scholar
  35. 35.
    Gu M, Warshawsky I, Majerus PW (1992) Cloning of a cytosolic megakaryocyte protein-tyrosine-phosphatase with sequence homology to retinaldehyde-binding protein and yeast SEC14p. Proc Natl Acad Sci USA 89: 2980–2984PubMedCrossRefGoogle Scholar
  36. 36.
    Roach T, Slater S, Koval M et al (1997) CD45 regulates Src family member kinase activity associated with macrophage integrin-mediated adhesion. Current Biology 7: 408–417PubMedCrossRefGoogle Scholar
  37. 37.
    Burns CM, Sakaguchi K, Appella E, Ashwell JD (1994) CD45 regulation of tyrosine phosphorylation and enzyme activity of src family kinases. J Biol Chem 269: 13594–135600PubMedGoogle Scholar
  38. 38.
    Yi T, Mui AL, Krystal G, Ihle JN (1993) Hematopoietic cell phosphatase associates with the Interleukin-3 (IL-3) receptor beta chain and down-regulates IL-3-induced tyrosine phosphorylation and mitogenesis. Mol Cell Biol 13: 7577–7586PubMedGoogle Scholar
  39. 39.
    Bignon JS, Siminovitch KA (1994) Identification of PTP1C mutation as the genetic defect in motheaten and viable motheaten mice: A step toward defining the roles of protein tyrosine phosphatases in the regulation of hemopoietic cell differentiation and function. Clin Immunol Immunopath 73: 168–179CrossRefGoogle Scholar
  40. 40.
    Dong Q, Siminovitch KA, Fialkow L et al (1999) Negative regulation of myeloid cell proliferation and function by the SH2 domain-containing tyrsoine phosphatase-1. J Immunol 162: 3220–3230PubMedGoogle Scholar

Copyright information

© Springer-Verlag Italia, Milano 2001

Authors and Affiliations

  • J. Kruger
  • T. Fukushima
  • G. P. Downey

There are no affiliations available

Personalised recommendations