Interleukin 3 alone does not support the proliferation of bone marrow cells from A/J mice: a novel system for studying the synergistic activities of IL‐3

Abstract

The number of colonies produced by bone marrow cells in response to interleukin 3 (IL-3) in soft agar cultures varies according to the strain of the donor mice. A/J, AKR, A.TH and A.TL bone marrow cells are particularly hyporesponsive, producing only occasional colonies in the presence of IL-3. Bone marrow cells from all strains of mice, including A/J, produce distinctively large colonies in response to the combination of IL-3 and macrophage colony stimulating factor (M-CSF). In cultures of A/J bone marrow cells, the synergy between IL-3 and M-CSF is further reflected in an increase in both the number and the variety of colonies produced. The increase in colony numbers may be due to the priming of a population of A/J colony-forming-cells (CFCs) by IL-3, enabling them to respond to M-CSF. In support of this notion, IL-3 enhanced the level of c-fms (M-CSF receptor) messenger RNA in cultures of A/J bone marrow cells. It is also possible that a subpopulation of CFCs requires both IL-3 and M-CSF as co-mitogens. The A/J strain provides a novel system for studying the mechanisms involved in the interaction between IL-3 and M-CSF in haemopoiesis.

Impaired interleukin-3 (IL-3) response of the A/J mouse is caused by a branch point deletion in the IL-3 receptor alpha subunit gene.

“…Impaired IL-3 response of bone marrow cells from the A/J mouse As previously shown by Morris et al (1990), IL-3 alone did not support granulocyte/macrophage (GM) colony formation from A/J-derived bone marrow cells, whereas IL-3 alone stimulated GM colony formation from C57BL/ 6-derived bone marrow cells (Figure lA). In contrast, GM-CSF or stem cell factor (SCF) alone stimulated colony formation of the A/J bone marrow cells to a level comparable with that of C57BL/6 bone marrow cells in GM colony assays ( Figure IA).…”

“…et al, 1979;Horland et al, 1980). In addition, based on the defective IL-3 response in Fl crosses between A/J and AKR mice, these two IL-3-non-responsive strains seem to be in a single complementation group (Morris et al, 1990). In addition, based on the defective IL-3 response in Fl crosses between A/J and AKR mice, these two IL-3-non-responsive strains seem to be in a single complementation group (Morris et al, 1990).…”

“…Interestingly, however, Morris et al (1990) showed that IL-3 alone does not support colony formation of bone marrow cells from A/J, AKR, A.TH or A.TL mouse strains, but IL-3 stimulates colony formation in the presence of macrophage CSF (M-CSF). Interestingly, however, Morris et al (1990) showed that IL-3 alone does not support colony formation of bone marrow cells from A/J, AKR, A.TH or A.TL mouse strains, but IL-3 stimulates colony formation in the presence of macrophage CSF (M-CSF).…”

“…Furthermore, two other strains, RF and NZB, were also reported to show a defective response to WEHI-3H cell supematant, a major source of IL-3 (Kincade M.ichihara et a!. Genetic crossing experiments proved that the defective IL-3 response of A/J and AKR mice was recessive to the trait of IL-3responsive mouse strains (Morris et al, 1990). Genetic crossing experiments proved that the defective IL-3 response of A/J and AKR mice was recessive to the trait of IL-3responsive mouse strains (Morris et al, 1990).…”

IL-3 and CSF-1 Interact to Promote Generation of CD11c+ IL-10-Producing Macrophages

“…IL-3 stimulates ex vivo generation of MCs, macrophages, basophils and CD11c + cells in mouse bone marrow (BM) [9], [10]. The hematopoietic effect of IL-3 has been shown to be strain-specific [11]. In contrast to IL-3, CSF-1 or macrophage colony-stimulating factor (M-CSF) is produced in the steady state, with a much more restricted hematopoietic coverage, primarily regulating development of the monocyte lineage [12], [13], [14], and has been reported to have a role in developing dendritic cells (DCs) [15].…”