Interleukin 5, produced primarily by activated T cells and mast cells, has diverse biological effects on a variety of cell types. Human IL-5 is a potent eosinophil differentiation and activation factor in vivo and in vitro. Additionally, it has also been reported that IL-5 can stimulate the proliferation and/or differentiation of basophils and B cells. The multiple effects of IL-5 are mediated by binding of the cytokine to specific cell surface receptors expressed on target cells. As is the case with many other cytokines, the functional high-affinity receptor for IL-5 is a complex consisting of a ligand binding subunit ( alpha chain) and a second subunit ( beta chain) that can modulate the ligand binding affinity of the receptor complex. In the case of IL-5, the beta subunit is shared with the high affinity receptor complexes for IL-3 and GM-CSF. The beta chain does not bind any of the cytokines in question but is indispensable for the cytokine-mediated signaling.
cDNA clones for the alpha chain (IL-5 R alpha ) of both the mouse and human high affinity IL-5 receptor complexes have been isolated. Human and mouse IL-5 R alpha are both members of the hematopoietin receptor superfamily characterized by the presence of the WSXWS, and a four cysteine residue motif in the extracellular domain of the transmembrane protein. In addition to the cDNA clone encoding the full-length transmembrane protein, cDNA clones that arise from alternative splicing and that encode soluble secreted forms of IL-5 R alpha have been isolated from mouse as well as human cells. A naturally-occurring soluble form of the IL-5 R alpha has been detected in biological fluids of autoimmune-prone mice and mice bearing chronic B cell leukemia (BCL1).
A recombinant human IL-5 soluble receptor alpha has been shown to bind the human IL-5 dimer in a 1:1 ratio and acts as a human IL-5 antagonist. This molecule inhibits the proliferation of IL-5-dependent cell lines and blocks human umbilical cord blood eosinophil differentiation.
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