S. Rounds et al., EFFECTS OF ENDOTOXIN INJURY ON ENDOTHELIAL-CELL ADENOSINE METABOLISM, The Journal of laboratory and clinical medicine, 123(2), 1994, pp. 309-317
Citations number
45
Categorie Soggetti
Medical Laboratory Technology","Medicine, General & Internal
Adenosine is a potent autocoid that acts as a vasodilator and modulato
r of inflammatory responses. Endothelial cells possess several mechani
sms for altering circulating levels of adenosine and are capable of re
lease of adenosine metabolites. We used cultured bovine aortic and mai
n pulmonary arterial endothelial cells to determine whether endotoxin
can alter adenosine uptake or release of adenosine metabolites. We fou
nd that 24 hours, but not 6 hours, of incubation with endotoxin caused
endothelial cell injury, as assessed by cell detachment and chromium
51 release. Despite this injury the extent of [H-3]adenosine uptake wa
s unchanged. Using thin-layer chromatography to identify adenosine and
its metabolites, we found that [3H]adenosine was primarily metabolize
d into intracellular hypoxanthine and adenine nucleotides. After 1, 6,
and 24 hours of incubation with endotoxin there was an increase in ex
tracellular adenosine metabolites, which was accompanied by decreases
in the level of intracellular adenosine 5'-triphosphate. The appearanc
e of adenosine metabolites in culture supernatants was a more sensitiv
e measure of endothelial cell injury than Cr-51 release or adherent ce
ll number. The extracellular purine metabolite observed in response to
endotoxin injury was mainly hypoxanthine. Our findings suggest that h
ypoxanthine release is an early event in endotoxin-induced endothelial
cell injury. Because hypoxanthine may act as a substrate for xanthine
oxidase, resulting in toxic oxidant production, its release has the p
otential of exacerbating vascular injury caused by endotoxin.