Role of kidney in the catabolic clearance of human platelet antiheparin
proteins from rat circulation
CP Bastl, J Musial, M Kloczewiak, J Guzzo, I Berman and S Niewiarowski
Stimulated platelets release at least two antiheparin proteins: platelet
factor 4 (PF4) and low affinity platelet factor 4 (LA-PF4) from which
beta-thromboglobulin (beta TG) is derived. We have found previously marked
elevation of LA-PF4/beta TG antigen in platelet poor plasma of patients
with chronic renal failure, whereas levels of PF4 remained normal.
Therefore, we examined the role of the kidneys in the metabolic clearance
of LA-PF4/beta TG and PF4. The supernates of aggregates of
thrombin-stimulated human platelets were injected into sham operated
control rats, nephrectomized rats, and into rats with acute ureteral
ligation. The disappearance of human LA-PF4/beta TG antigen and PF4 in rat
plasma determined by specific radioimmunoassays followed biphasic
exponential curves. The half-lives (t1/2) for the fast and slow components
of LA-PF4 in control rats were 6.4 and 68.4 min. Nephrectomy significantly
increased these times to 9.7 and 144 min, while ureteral ligation resulted
in no significant change. Comparison of the level of LA-PF4/beta TG antigen
and of creatinine in aorta and in renal vein showed 25%-30% extraction of
these compounds by the kidney. Less than 0.1% of the total LA-PF4 antigen
injected was recovered in the urine of control rats. In contrast to these
results, the clearance of PF4 was not affected by nephrectomy. In
conclusion: (1) functional renal tissue is necessary for normal clearance
of LA- PF4/beta TG, but renal excretion does not play a major role in its
elimination suggesting that the protein is catabolized by the kidney; and
(2) catabolic clearance of PF4 does not depend on functioning kidney
tissue.
Volume 57,
Issue 2,
pp. 233-238,
02/01/1981
Copyright © 1981 by The American Society of Hematology
