Augmentation of neutrophilic granulocyte progenitors in the bone marrow of mice with tumor-induced neutrophilia: cytochemical study of in vitro colonies

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.