Factors Influencing Proliferation and Histamine Content of Cultured Human Bone Marrow Cells

Abstract

Various human lymphokines such as semipurified human interleukin 3 (IL 3), recombinanthuman IL 3, granulocyte colony stimulating factor (G-CSF), and recombinant human interleukin 4 (IL 4) stimulated growth of human bone marrow cells, but from all these factors tested, only IL 3 by itself was able to cause an increase in histamine content. Fibroblast monolayers as well as factors in their supernatants also increased proliferation and histamine content of bone marrow cells. Concentrated supernatants (Mr > 10,000) also inhibited cell proliferation and induced histamine content. The same fraction concentrated on a Mr cut-off > 50,000 enhanced cell growth and the total histamine content per culture. Thus, fibroblast supernatants contained both growth promoting and inhibitory factors. However, using the rat basophilic leukemia (RBL) cell line as a test system for such fibroblast-derived differentiation factors, we showed that if cell proliferation was inhibited, histamine content was also enhanced. Furthermore, certain drugs known to inhibit cell division, such as sodium butyrate or hydroxyurea, were also found to cause an increase in histamine content of RBL cells. Thus, our data demonstrate that basophil/mast cell differentiation, in terms of augmentation of cellular histamine levels, may be achieved by exposure to certain growth-inducing cytokines, factors inhibiting proliferation or pharmacological agents which inhibit cell proliferation.