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, an
d 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 tis
sue and epithelial cells, were measured. XO was localised by histochemical
staining.
Results-PAF dose dependently induced an increase in XO activity, predominan
tly 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 activat
ion 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 substan
tially inhibited intestinal neutrophil sequestration induced by high dose (
but not low dose) PAF.
Conclusions-PAF rapidly activates intestinal XO through proteolytic XD-XO c
onversion, predominantly in the ileal epithelium. This effect is mediated b
y neutrophils. XO activation promotes PAF induced polymorphonuclear leucocy
te sequestration in the intestine.