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Fructose‐1,6‐biphosphate and nucleoside pool modifications prevent neutrophil accumulation in the reperfused intestine
Author(s) -
Sola Anna,
Panés Julián,
Xaus Carme,
Hotter Georgina
Publication year - 2003
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0602299
Subject(s) - nucleoside , biology , biochemistry , in vivo , xanthine , ischemia , adenosine , reperfusion injury , pharmacology , endogeny , adenosine deaminase , medicine , enzyme , microbiology and biotechnology
Fructose‐1,6‐biphosphate (F16BP) attenuates ischemia/reperfusion (I/R) injury by inhibiting microvascular leukocyte adhesion or reducing neutrophil‐derived oxygen free‐radical production, but the causes of this action, the mechanisms in vivo, and the possible implication of nucleoside pool modifications are still controversial issues. We explored whether F16BP's inhibition of free‐radical production and neutrophil recruitment is a result of its effect on adenosine (Ado) accumulation during intestinal I/R injury. The effects of F16BP administration were tested on the nucleotide/nucleoside metabolism at the end of the ischemic period and on microvascular neutrophil recruitment and free‐radical production after reperfusion in vivo, in the presence or absence of Ado deaminase (ADA). Infusion of F16BP markedly increaed endogenous Ado, decreased xanthine accumulation during the ischemic period, and inhibited neutrophil recruitment and subsequent neutrophil free‐radical generation during reperfusion. Administration of ADA reversed these processes. The results provide strong evidence that F16BP prevents neutrophil accumulation and neutrophil free‐radical generation during intestinal I/R by a key mechanism that modifies the nucleoside pool, leading to an endogenous accumulation of Ado and to a reduction of xanthine during ischemia.