THE LEUKEMIA INHIBITORY FACTOR AND ITS RECEPTOR

This chapter focuses on the leukemia inhibitory factor (LIF) and its receptor that exemplifies many features of cytokine biology. The gene encoding LIF has been cloned and its product characterized extensively; LIF binds to receptors on responsive cells with high and low affinity and the molecular basis for the two types of receptors are determined. Many protein factors that affect the growth and differentiation of mammalian cells are characterized and are collectively termed growth factors or cytokines. The biochemical rationale for the two forms of LIF, one soluble and the other immobilized, are discussed and the suggestion made that the immobilized LIF may be deposited as a topological or temporal signal in the developing embryo. LIF expression fluctuates in different tissues during development, there being more in adult brain than in embryonic brain and more in day 1 postnatal heart than in adult heart. The development of primordial germ cells is also affected by LIF. A combination of LIF and steel factor improves primordial germ cell survival and proliferative capacity in vitro. There are two clinically interesting systems in which LIF is demonstrated to be active—namely, inflammation and cachexia. Serum LIF levels are elevated in mice treated with bacterial lipopolysaccharide, and LIF is demonstrated to be identical in structure and function to hepatocyte-stimulating factor III that causes the release of acute-phase plasma proteins (APPs). © 1993, Academic Press Inc. All rights reserved.