High adenosine and deoxyadenosine concentrations in mononuclear cells of hemodialyzed patients.
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.
Sampol
Jerome
J
UMR CNRS 6560, Faculté de Médecine Secteur Nord, Marseille, France.|Service de Néphrologie, Hôpital Sainte Marguerite, Marseille, France.
Dussol
Bertrand
B
Service de Néphrologie, Hôpital Sainte Marguerite, Marseille, France.|Centre d'Investigation Clinique, Hôpital Sainte Marguerite, Marseille, France.
Fenouillet
Emmanuel
E
UMR CNRS 6560, Faculté de Médecine Secteur Nord, Marseille, France.
Capo
Christian
C
CNRS UPRESA 6020 Unité des Rickettsies, Marseille, France.
Mege
Jean-Louis
JL
CNRS UPRESA 6020 Unité des Rickettsies, Marseille, France.
Halimi
Gilles
G
UMR CNRS 6560, Faculté de Médecine Secteur Nord, Marseille, France.
Bechis
Guy
G
UMR CNRS 6560, Faculté de Médecine Secteur Nord, Marseille, France.
Brunet
Philippe
P
Service de Néphrologie, Hôpital Sainte Marguerite, Marseille, France.|Centre d'Investigation Clinique, Hôpital Sainte Marguerite, Marseille, France.
Rochat
Herve
H
Service de Néphrologie, Hôpital Sainte Marguerite, Marseille, France.|Centre d'Investigation Clinique, Hôpital Sainte Marguerite, Marseille, France.
Berland
Yvon
Y
Service de Néphrologie, Hôpital Sainte Marguerite, Marseille, France.|Centre d'Investigation Clinique, Hôpital Sainte Marguerite, Marseille, France.
Guieu
Regis
R
UMR CNRS 6560, Faculté de Médecine Secteur Nord, Marseille, France.|Laboratoire de Biochimie, Hôpital de la Timone, Marseille, France.
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
D003839:Deoxyadenosines; D009705:Nucleosides; D007371:Interferon-gamma; D000248:Adenosine Kinase; D000241:Adenosine