Local and Systemic Control of Granulocytic and Macrophage Progenitor Cell Regeneration After Irradiation

Abstract

Agar cultures of C57BL bone marrow cells were used to determine colony stimulating factor (CSF) and serum CSF‐inhibitor levels in C57BL and BALB/c mice following irradiation. Whole‐body irradiation caused an acute, dose‐dependent, rise in serum CSF levels and fall in CSF‐inhibitor levels. The regeneration of granulocytic and macrophage progenitor cells (in vitro CFCs) in the femur after 250 rads whole‐body irradiation was preceded or paralleled by a fall in serum CSF‐inhibitors and a dramatic rise in the capacity of bone‐adherent cells in the marrow (‘stromal cells’) to produce material with colony‐stimulating activity. No comparable changes were observed in the activity of marrow haemopoietic cells during regeneration or in the lungs or spleen. A similar rise in the activity of bone‐adherent cells was observed in shielded femurs during regeneration of in vitro CFCs. Regeneration of granulocytic and macrophage progenitor cells following irradiation may be regulated by fluctuations in circulating CSF‐inhibitor levels and local production of CSF within the marrow cavity.

Hematological characterization of congenital osteopetrosis in op/op mouse. Possible mechanism for abnormal macrophage differentiation.

“…Fibroblastoid cells that form adherent cell colonies in liquid cultures of bone marrow cells are the precursor cells of bone stromal tissue (20,31,32). In vivo, the bone stromal tissue is one of the best sources of CSA (29,33,34). In cultures of marrow or spleen cells from normal mice, macrophages adhere directly to fibroblastoid cells.…”

Effect of Hypertransfusion on Granulopoiesis in Bone Marrow Depression: Studies in the Irradiated Mouse

“…The animal model employed for the study consisted of the C57B mouse which had been exposed to 3 50 rads whole body irradiation. This radiation dose reduces the multipotential and committed myeloid stem cell populations to about 5% of normal, and produces a phase of pancytopenia of a severity just below the threshold where deaths occur from complications of marrow depression (McCulloch & Till, 1962;Chan & Metcalf, 1973). Hypertransfusion was carried out after irradiation had been completed by administration of single or multiple intraperitoneal transfusions.…”

In vitro production of granulocyte–macrophage colony‐stimulating activity by murine bone marrow and spleen following vinblastine administration IN VIVO

“…Demonstration of an in vivo role for CSA had been hampered by the lack of a sufficient quantity of pure material to conduct in-depth studies. However, several indirect lines of evidence suggest that CSA may play a role in the maintenance of normal circulating levels of granulocytes and macrophages (Asano et al, 1977;Moore et al, 1974;Chan and Metcalf, 1973;Karp et al, 1983;Metcalf and Stanley, 1971;Winton et al. 1981;Shadduck and Nagabhushanam, 1971;Broxmeyer et al, 1985).…”