抄録
The pathogenetic importance of oxygen intermediates (O.I.) which are highly reactive has been recognized recently. The present paper reports that human vascular damage may be mediated by granulocytes and this damage was inhibited by scavengers of O.I.. The cultured human endothelial cells (EC) derived from umbilical cord vein were used as in vitro model of the vessel. The hypoxanthine-xanthine-oxidase (HPX-XOD) system was used as the model of granulocytes which generate O.I.. EC damage was determined by trypan blue dye exclusion test or microcytotoxicity assay. EC damage in HPX-XOD system was marked and this damage was not inhibited by adding superoxide dismutase (SOD) alone. The catalase significantly inhibited EC damage, but incompletely. Simultaneous addition of both SOD and catalase in the system completely inhibited EC damage. Various concentrations of commercial H2O2 showed dose dependent EC damage. These results suggest that H2O2 is most highly destructive for EC and simultaneous additon of the scavengers was most effective for the inhibition of EC damage. The human granulocyte lysate which is rich in lysosomal enzymes, but does not generate O.I. showed EC damage in dose dependent fashion. The interaction of granulocyte and SLE serum leading to the release of O.I. into extracellular fluid may cause in vivo vascular damage. The granulocytes, on the other hand, may act to defend such oxygen toxicity in vivo (negative feed back system), releasing scavengers into plasma. The O.I. did neither affect Fe receptors on the granulocytes nor have any influence on the surface receptors of EC. The deposition of immune complexes in EC which had been reported experimentally and clinically seemed to be due to nonspecific micropinocytotic mechanism, not mediated by specific receptors.
