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Inflammation
The role of xanthine oxidase in platelet activating factor induced intestinal injury in the rat
  1. X W Qua,
  2. R A Rozenfelda,
  3. W Huanga,
  4. G B Bulkleyb,
  5. W Hsueha
  1. aDepartment of Pathology, Children’s Memorial Medical Center, Northwestern University Medical School, Chicago, Illinois, USA, bDepartment of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  1. Dr W Hsueh, Department of Pathology, Children’s Memorial Hospital, Chicago, IL 60614, USA.

Abstract

Background Xanthine oxidase (XO) is an important source of reactive oxygen species in the small intestine.

Aims To examine the interaction of platelet activating factor (PAF), XO, and neutrophils in mediating intestinal injury in rats.

Methods Two doses of PAF were used to induce either reversible hypotension, or irreversible shock with intestinal necrosis. The activities of XO, and its precursor xanthine dehydrogenase (XD), in both the whole intestinal tissue and epithelial cells, were measured. XO was localised by histochemical staining.

Results PAF dose dependently induced an increase in XO activity, predominantly in the ileal epithelium, without altering the total activity of XD+XO. Most of the XD to XO conversion was via proteolysis. PAF induced XO activation and intestinal injury were prevented by prior neutrophil depletion. PAF induced XO activation is probably not due to reperfusion, as XO activation preceded the recovery of mesenteric flow. Allopurinol pretreatment substantially inhibited intestinal neutrophil sequestration induced by high dose (but not low dose) PAF.

Conclusions PAF rapidly activates intestinal XO through proteolytic XD-XO conversion, predominantly in the ileal epithelium. This effect is mediated by neutrophils. XO activation promotes PAF induced polymorphonuclear leucocyte sequestration in the intestine.

  • xanthine dehydrogenase
  • reactive oxygen species
  • leucocyte adhesion
  • neutrophils
  • shock

  • Abbreviations

    MPO
    myeloperoxidase
    PAF
    platelet activating factor
    PMN
    polymorphonuclear leucocyte
    ROS
    reactive oxygen species
    XD
    xanthine dehydrogenase
    XO
    xanthine oxidase
    DMSO
    dimethylsulphoxide
    WBC
    white blood cell
    DTT
    dithiothreitol
    SMA
    superior mesenteric artery
    PMSF
    phenylmethylsulphonyl fluroide
    I/R
    ischaemia/reperfusion

    • https://doi.org/10.1136/gut.44.2.203

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    • Abbreviations

      MPO
      myeloperoxidase
      PAF
      platelet activating factor
      PMN
      polymorphonuclear leucocyte
      ROS
      reactive oxygen species
      XD
      xanthine dehydrogenase
      XO
      xanthine oxidase
      DMSO
      dimethylsulphoxide
      WBC
      white blood cell
      DTT
      dithiothreitol
      SMA
      superior mesenteric artery
      PMSF
      phenylmethylsulphonyl fluroide
      I/R
      ischaemia/reperfusion
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