Lipopolysaccharide alters nucleotidase activities from lymphocytes and serum of rats.
ATP exerts a proinflammatory role and induces cytokine release by acting at P2X(7) receptors. The product of ATP hydrolysis is the nucleoside adenosine, an important immunomodulator. The main source of extracellular adenosine is the hydrolysis of extracellular ATP by a group of ecto-enzymes: ENTPDase family, NPP family and ecto-5'-nucleotidase. Considering the role of ATP and adenosine in inflammatory processes, we investigated the effect of lipopolysaccharide on ectonucleotidases activities and expression in lymphocytes from mesenteric lymph nodes and serum of rats, in order to better understand the involvement of extracellular nucleotide hydrolysis in an endotoxemia model. We observed significant changes on nucleotidase activities from lymphocytes and serum of rats after in vitro and in vivo exposure to LPS. In vitro results have shown an increase on nucleotide hydrolysis in lymphocytes and a decrease on the enzyme activity of NPP in blood serum. In vivo, we observed an increase on nucleotide hydrolysis in lymphocytes and a decrease in the hydrolysis of all nucleotides tested in blood serum. After 24 and 48 h of LPS treatment, there was a reduction in NTPDase1, 2, 3 and ecto-5'-nucleotidase transcripts. These results suggest that there is a time-dependent enhancement of extracellular nucleotides metabolism in lymphocytes and blood serum after the induction of an endotoxemic model. The changes observed suggest that these enzymes can act in the regulation of extracellular nucleosides and nucleotides in a model able to trigger inflammatory process.
Vuaden
Fernanda Cenci
FC
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600, Anexo, 90035-003, Porto Alegre, RS, Brazil.
de Paula Cognato
Giana
G
Bonorino
Cristina
C
Bogo
Maurício Reis
MR
de Freitas Sarkis
João José
JJ
Bonan
Carla Denise
CD
D000227:Adenine Nucleotides / Q000097:blood / Q000378:metabolism; D000818:Animals; D001081:Apyrase / Q000037:antagonists & inhibitors* / Q000097:blood / Q000235:genetics; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000201:enzymology*; D004926:Escherichia coli / Q000276:immunology; D015870:Gene Expression / Q000187:drug effects; D006868:Hydrolysis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009708:Nucleotidases / Q000037:antagonists & inhibitors* / Q000097:blood / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar
D000227:Adenine Nucleotides; D008070:Lipopolysaccharides; D009708:Nucleotidases; D001081:Apyrase