Studies on the Regulation of Granulopoiesis

Abstract

Summary. Tritiated thymidine autoradiography was used to study the control of granulocyte production and release using the irradiated leg shielded mouse as an experimental model. Neutropenia resulted in a shortening of 24–36 hr in the mean transit time through the non‐proliferating granulocyte compartment. There was little difference between neutropenic and control animals in labelling indices of the cells in the proliferative granulocyte compartments, which suggests that the granulocytic hyperplasia observed in the neutropenic mice was predominantly due to differentiation of morphologically unrecognizable precursor cells rather than increased proliferation of morphologically recognizable cells. The persistence of a labelling index of approximately 60% in the myeloblast‐promyelocyte compartment 24 hr after injection suggests that these precursor cells were rapidly proliferating.

Macrocolony Assays in the Rat of Allogeneic Y-P388 and W-256 Tumour Cells Injected Intravenously: Dependence of Colony Forming Efficiency on Age of Host and Immunity

“…Other workers have provided evidence that ALS destroys or neutralizes the functions of a variety of circulating and fixed tissue cells other than lymphocytes, including other leucocytes, splenic giant cells and even epithelial and connective tissue elements (see Yoffey and Courtice, 1970). The glomerular mesangeitis produced rapidly by the nephrotoxic action of ALS on the kidney (Lindquist et al, 1969) (Puck and Marcus, 1956) and in vivo (Revesz, 1958; van den Brenk and Shlarpington, 1971b), a "leucocyte stimulating factor " in granulopoiesis (Metcalf,1 970) which is also present in serum of irradiated mice (Morley et al, 1971;Rickard et al, 1971a, b), a portal blood factor acting as a hlutmoral agent in liver regeneration (Fisher et al, 1971), a HeLa cell stimulating factor in normal calf serum (Salmon and Hosse, 1971) and polyaminies derived from ornithine in tissues which stimulate normal aand neoplastic growth (Tabor and Tabor, 1964;Bucher and Malt, 1971 (Fig. 7).…”

Human leukaemia: recent tissue culture studies on the nature of myeloid leukaemia

“…Germ-free mice have abnormally low serum CSF levels (Metcalf, Foster and Pollard, 1967a), emphasizing the role of bacterial products in provoking CSF production by the tissues. Furthermore, serum CSF levels in germ-free mice are not elevated by whole-body irradiation, as occurs following irradiation of conventional mice (Morley et al, 1971. It seems possible therefore that the capacity of C-type viruses to induce myeloid leukaemia development may be dependent on a sufficient proliferative pressure being applied by CSF on the virus-altered granulopoietic cells to force the emergence of an abnormal (leukaemic) subpopulation.…”

“…Studies of CSF levels in mice and humans during fluctuations in the level of granulopoiesis or monocyte formation, together with observations on the in vivo effects of injected preparations of CSF, suggest that CSF is a humoral regulator of granulopoiesis and monocyte formation (Bradley et al, 1969;Metcalf and Stanley, 1971;Metcalf and Moore, 1971;Morley et al, 1971).…”

Stimulation of granulocytic colony formation in agar diffusion chambers implanted in cyclophosphamide pretreated mice

“…Fried et al (1973) reported that this effect was due to modification of the marrow micro-environment, although a possible humoral effect was not ruled out. Morley et al ( 1971) suggested that there was a close relationship between the colony stimulating activity of serum and the level of granulocytopenia in irradiated mice. The results presented here do not support this proposal since higher serum CSF levels were detected in control mice in the absence of granulocytopenia.…”