Parathyroid hormone inhibits B cell proliferation: implications in chronic renal failure.
B cell proliferation is impaired in patients with chronic renal failure, but the mechanisms underlying this defect are not known. Lymphocytes have receptors for parathyroid hormone, and it is possible that the state of secondary hyperparathyroidism of renal failure is responsible for the B cell defect. Our studies were designed to (a) examine T cell-independent B cell proliferation [3H)thymidine incorporation) induced by Staphylococcus aureus Cowan 1 after 5 days of culture, (b) evaluate the effect of parathyroid hormone on S. aureus Cowan I-induced B cell proliferation, and (c) investigate the mechanisms through which parathyroid hormone may exert its effect on B cell proliferation. Lymphocytes were obtained from 37 normal subjects and 21 dialysis patients. S. aureus Cowan I induced significant stimulation (P less than 0.01) of the proliferation of B cells from both groups, but the effect was smaller on B cells from dialysis patients (10.0 x 10(3) +/- 1.4 x 10(3) cpm) than on those from normal subjects (21.8 x 10(3) +/- 2.0 x 10(3) cpm). Both the intact molecule of parathyroid hormone (1-84 PTH) and its amino-terminal fragment (1-34 PTH) caused significant inhibition of proliferation of B cells from normal subjects in a dose-dependent manner, with the effect being significantly greater (P less than 0.01) with an equimolar concentration of 1-84 PTH than that of 1-34 PTH. Inactivation of 1-84 PTH by oxidation abolished most of its inhibitory effect on B cell proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)
Alexiewicz
J M
JM
Department of Medicine, University of Southern California, School of Medicine, Los Angeles 90333.
Klinger
M
M
Pitts
T O
TO
Gaciong
Z
Z
Linker-Israeli
M
M
Massry
S G
SG
D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D005260:Female; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000209:etiology / Q000276:immunology; D066298:In Vitro Techniques; D007676:Kidney Failure, Chronic / Q000150:complications / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000276:immunology; D013936:Thymidine / Q000378:metabolism
D010281:Parathyroid Hormone; D005576:Colforsin; D000242:Cyclic AMP; D013936:Thymidine