Soluble cytokine receptors

Abstract

HE WORD “HORMONE” comes from the Greek, meaning to set in motion, whereas “humoral” comes from the Latin for ‘‘liquid.’’ Classical hormones are delivered in the blood “to set in motion” target cell proliferation or functional activation. Therefore, humoral specificity depends on the hormone’s ability to interact only with cells expressing the appropriate receptor. This receptor-ligand interaction is central to maintaining and regulating biologic function at the cell, tissue, organ, and organism level. The response evoked in the individual cell requires the association of a soluble ligand to its cognate cellular receptor. More recent modifications of the traditional endocrinologic concepts, where the target tissue lies at a distance from the secreted hormone, have included paracrine, juxtacrine, and autocrine models to describe ligand-receptor interactions over short distances. Regulation of cellular responses in this broadened paradigm occurs in cells that secrete graded amounts of hormone and in the target cells which control the number of receptors presented and can modify signal transduction after ligand-receptor association. In all models, hormonal specificity depends on the responding cell displaying the cognate receptor. In the hematopoietic system, lineage commitment is defined by progenitor cell expression of receptors for lineage-restricted hormones.’ The term “cytokine” has come to be used for a diverse group of glycoprotein growth factors, inflammatory mediators, and hematopoietic regulators that are distinct from the more classical hormones secreted by the glands of the endocrine system. The appreciation that many membrane-bound receptors are also synthesized as secreted soluble forms has led to important modifications in our understanding of ligand-receptor interactions and hormone and cytokine action in general.’ These mobile, soluble receptors may modify ligand concentrations by serving as stabilizing binding proteins, may downregulate membrane receptor number as a mechanism of genesis, and may specifically inhibit ligandreceptor association in the extracellular space. Soluble receptors also can confer on cells and tissues the ability to respond to ligands for which they do not normally express the cognate receptor. In this review, we discuss the mechanisms by which soluble receptors are generated, the regulation of soluble receptor expression, the ways that soluble receptors modify receptor-ligand interactions, and how soluble receptors may impact on clinical medicine. Blood, Vol 87, No 3 (February l), 1996: pp 847-857 MECHANISM OF SOLUBLE RECEPTOR GENERATION