title: High adenosine and deoxyadenosine concentrations in mononuclear cells of hemodialyzed patients.
abstract: Infections are one of the most important complications of hemodialysis (HD). The high concentrations of adenosine (Ado) and of its metabolites during HD may contribute to the dialysis-induced immune deficiency through their known ability to alter lymphocyte function. The influence of HD on Ado metabolism was assessed in mononuclear cells through the measurement of (1) the concentrations of nucleosides in mononuclear cells and (2) the activities of mononuclear cell Ado deaminase (MCADA) and Ado kinase, two enzymes involved in Ado concentration regulation. Nine end-stage renal failure hemodialyzed patients (five men and four women; mean age, 69 +/- 10 yr) and eight healthy volunteers (four men and four women; mean age, 53 +/- 19 yr) were included in the study. Before HD, Ado, deoxyadenosine, and inosine concentrations were respectively 2.9-, 2.5-, and 2.5-fold higher in mononuclear cells of patients than in healthy volunteers. During HD, Ado concentration decreased by 34%, whereas inosine concentration increased by 27%. Before HD, MCADA activity level was 2.1-fold lower in patients than in control subjects. After HD, MCADA activity increased by nearly 50% but remained lower than in control subjects. Ado kinase activity level of patients did not differ from that of control subjects and was unchanged by HD. The influence of Ado on in vitro mononuclear cell proliferation and interferon-gamma production also was evaluated. Ado inhibited cell proliferation and interferon-gamma production in a dose-dependent manner, and these inhibitions were stronger for patients than for healthy volunteers. The high concentrations of Ado and deoxyadenosine in mononuclear cells and the low MCADA activity level likely are involved in the immune defect of patients who are undergoing HD.
authors.affiliation: UMR CNRS 6560, Faculté de Médecine Secteur Nord, Marseille, France.|Service de Néphrologie, Hôpital Sainte Marguerite, Marseille, France.
authors.forename: Jerome
authors.initials: J
authors.lastname: Sampol
authors.affiliation: Service de Néphrologie, Hôpital Sainte Marguerite, Marseille, France.|Centre d'Investigation Clinique, Hôpital Sainte Marguerite, Marseille, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Dussol
authors.affiliation: UMR CNRS 6560, Faculté de Médecine Secteur Nord, Marseille, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Fenouillet
authors.affiliation: CNRS UPRESA 6020 Unité des Rickettsies, Marseille, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Capo
authors.affiliation: CNRS UPRESA 6020 Unité des Rickettsies, Marseille, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Mege
authors.affiliation: UMR CNRS 6560, Faculté de Médecine Secteur Nord, Marseille, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Halimi
authors.affiliation: UMR CNRS 6560, Faculté de Médecine Secteur Nord, Marseille, France.
authors.forename: Guy
authors.initials: G
authors.lastname: Bechis
authors.affiliation: Service de Néphrologie, Hôpital Sainte Marguerite, Marseille, France.|Centre d'Investigation Clinique, Hôpital Sainte Marguerite, Marseille, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Brunet
authors.affiliation: Service de Néphrologie, Hôpital Sainte Marguerite, Marseille, France.|Centre d'Investigation Clinique, Hôpital Sainte Marguerite, Marseille, France.
authors.forename: Herve
authors.initials: H
authors.lastname: Rochat
authors.affiliation: Service de Néphrologie, Hôpital Sainte Marguerite, Marseille, France.|Centre d'Investigation Clinique, Hôpital Sainte Marguerite, Marseille, France.
authors.forename: Yvon
authors.initials: Y
authors.lastname: Berland
authors.affiliation: UMR CNRS 6560, Faculté de Médecine Secteur Nord, Marseille, France.|Laboratoire de Biochimie, Hôpital de la Timone, Marseille, France.
authors.forename: Regis
authors.initials: R
authors.lastname: Guieu
mesh_terms: D000241:Adenosine / Q000097:blood* / Q000494:pharmacology; D000248:Adenosine Kinase / Q000097:blood; D000368:Aged; D000369:Aged, 80 and over; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D003839:Deoxyadenosines / Q000097:blood*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology; D009705:Nucleosides / Q000097:blood; D009994:Osmolar Concentration; D012016:Reference Values; D006435:Renal Dialysis
chemical_list: D003839:Deoxyadenosines; D009705:Nucleosides; D007371:Interferon-gamma; D000248:Adenosine Kinase; D000241:Adenosine