Abnormalities of the Hematopoietic Regulatory Network
Part of the
Advances in Experimental Medicine and Biology
book series (AEMB, volume 34)
It is now widely recognized that mononuclear phagocytes play a major role in regulating the production of hematopoietic growth factors by a variety of cell types1–17. As shown in Fig. 1, two monokines, interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF) are known to induce the expression of G- and GM-CSF genes in fibroblasts and in endothelial cells7,9,13,15 . Such observations have supported our notion that mononuclear phagocytes may serve as pivotal regulatory cells in growth factor gene expression12. The principal hurdle to be overcome is the uncertainty surrounding the biological relevance of these findings. This is a legitimate concern in view of the highly reductionistic design of the studies used in support of this model. For example, studies in our laboratory begin with the purification and culture, independently of other collaborating cell populations, of peripheral Blood monocytes in complete tissue culture medium to generate monocyte conditioned medium (MCM), followed by the introduction of serial dilutions of that MCM to confluent cultures of stromal cells such as fibroblasts or endothelial cells, and the assay of the stromal cell supernatants for hematopoietic growth factors1–4,6,11,14,15. In such experiments, IL-1 secreted by mononuclear phagocytes, induces the expression of G- and GM-CSF genes7,9,15, a phenomenon which can be detected by using the fibroblast or endothelial cell supernatants in specific bioassays with neutralizing antibodies15, by using western blot analysis, and by measuring CSF gene transcripts by northern or Si nuclease analysis7,9,15 (Fig. 2).
KeywordsMononuclear Phagocyte Colony Growth Elderly Volunteer Hematopoietic Growth Factor Auxiliary Cell
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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© Plenum Press, New York 1988