Synthesis of beta 2-microglobulin in lymphocyte culture: role of hemodialysis, dialysis membranes, dialysis-amyloidosis, and lymphokines.
Dialysis-amyloidosis (A beta 2M) is a recently recognized chronic complication in long-term dialysis patients, apparently effecting 5% to 10% of all dialysis patients. In 1985, Gejyo et al (Biochem Biophys Res Commun 129:701-706, 1085) and Shirahama et al (Lab Invest 53:705-709, 1985) identified beta 2-microglobulin (beta 2-M) as the major constituent protein of this unique type of systemic amyloidosis. The specific pathogenesis of A beta 2M remains unknown, although beta 2-M has been clearly identified as playing a central role as the amyloidogenic protein. To investigate the factors responsible for in vitro beta 2-M synthesis, we studied beta 2-M production by lymphocyte cultures obtained from dialysis patients and grown under a variety of different conditions, and compared the results to a control group of subjects with normal renal function. We could not demonstrate any stimulatory influence on beta 2-M synthesis by the hemodialysis treatment, the type of dialysis membrane used, or the clinical presence of A beta 2M. Rather, dialysis membranes, sterilized with ethylene oxide or gamma rays, added to the lymphocyte cultures exerted a strong dose-dependent inhibitory effect on beta 2-M synthesis. From the results of this study, we conclude that peripheral blood lymphocytes in uremic patients synthesize beta 2-M normally and that the direct interaction between circulating lymphocytes and the dialysis membrane that occurs during hemodialysis does not seem to contribute directly to beta 2-M synthesis.
Campistol
J M
JM
Department of Nephrology, Hospital Clinic, University of Barcelona, Spain.
Molina
R
R
Bernard
D B
DB
Rodriguez
R
R
Mirapeix
E
E
Munoz-Gomez
J M
JM
Revert
L
L
D000328:Adult; D000368:Aged; D000686:Amyloidosis / Q000097:blood* / Q000209:etiology; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000628:therapy; D008214:Lymphocytes / Q000378:metabolism*; D008222:Lymphokines / Q000502:physiology*; D008297:Male; D008567:Membranes, Artificial; D008875:Middle Aged; D015999:Multivariate Analysis; D006435:Renal Dialysis / Q000009:adverse effects*; D015203:Reproducibility of Results; D001613:beta 2-Microglobulin / Q000096:biosynthesis*
D008222:Lymphokines; D008567:Membranes, Artificial; D001613:beta 2-Microglobulin