Augmentation of neutrophilic granulocyte progenitors in the bone marrow of
mice with tumor-induced neutrophilia: cytochemical study of in vitro
colonies
MY Lee and JL Lottsfeldt
Transplantation of CE mammary carcinoma into mice has been shown to produce
marked neutrophilia. Previous studies in vivo indicated a significant
increase in marrow neutrophil production in these mice, but regulatory
mechanisms of this neutrophilia have not been well understood. In order to
obtain information about neutrophil production mechanisms at the progenitor
cell level, the profile of marrow granulocyte-macrophage progenitors in
mice with neutrophilia induced by this tumor was quantitatively analyzed by
cytochemical staining of in vitro colonies to distinguish colonies of
neutrophils (N-colony), macrophages (M-colony), and mixed cells
(NM-colony). Cell cycle kinetics of progenitors were studied by in vivo
administration of cytocidal drugs. The absolute number of N-colonies in a
femur increased significantly and reached three times normal three to four
weeks after tumor implantation. The number of NM-colonies also increased
significantly by the fourth week, but the number of M-colonies was
unchanged. The number of N-colonies in a femur related directly to the
degree of neutrophilia. The increased number of N-colonies from the marrow
of tumor-bearing mice was not attributed to a different time course of
colony growth nor to a different sensitivity to CSA; instead, a
significantly larger fraction of neutrophilic progenitors from the
tumor-bearing mice were in active cell cycle than were those of normal
mice. The day 14 tumor-bearing mouse serum demonstrated N-colony
stimulating activity while the sera of normal mice and day 7 tumor- bearing
mice were inhibitory for in vitro colony growth. These studies demonstrated
an increase in the numbers and turnover rate of marrow neutrophilic
progenitors in CE tumor-induced neutrophilia, suggesting that this tumor
stimulates proliferation of these progenitors in vivo.
Volume 64,
Issue 2,
pp. 499-506,
08/01/1984
Copyright © 1984 by The American Society of Hematology