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Quantitation of erythropoietin-producing cells in kidneys of mice by in
situ hybridization: correlation with hematocrit, renal erythropoietin mRNA,
and serum erythropoietin concentration
ST Koury, MJ Koury, MC Bondurant, J Caro and SE Graber
Department of Medicine, Vanderbilt University, Nashville, TN 37232-2287.
In situ hybridization was used to quantitate the cells that produce
erythropoietin (EP) in the renal cortices of mice with varying severities
of acute anemia and of mice recovering from severe, acute anemia. The
number of EP-producing cells in the renal cortex increased in an
exponential manner as hematocrit was decreased. Individual EP- producing
cells had very similar densities of silver grains in autoradiograms
regardless of whether they were from normal mice or from slightly,
moderately or severely anemic animals. With increasingly severe anemia,
total renal EP mRNA levels and serum EP concentrations showed increases
that correlated with the number of renal EP-producing cells. These results
indicate that as mice become more anemic, additional cells are recruited to
produce EP rather than the cells already producing EP being stimulated to
increase their individual production. In mildly and moderately anemic
animals, small clusters of EP-producing cells were found in the inner
cortex with large areas of cortex containing no EP-producing cells. In
severely anemic mice, EP- producing cells were found throughout the inner
cortex with only a very few found scattered in the outer cortex and outer
medulla. The data indicate that only a subset of total renal interstitial
cells produce EP. During recovery from severe, acute anemia, the numbers of
EP- producing cells decreased exponentially as hematocrits rose and
correlated with decreases in total renal EP mRNA and serum EP
concentrations. These results suggest that following an acute blood loss
and during the recovery from a blood loss, the capacity to deliver oxygen,
as represented by hematocrit, is the major regulator of EP production.
Volume 74,
Issue 2,
pp. 645-651,
08/01/1989
Copyright © 1989 by The American Society of Hematology

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