Increased Growth Promoting But Not Mast Cell Degranulation Potential of a Covalent Dimer of c-Kit Ligand

Autor: Nocka, Karl H., Levine, Beth A., Ko, Jone-Lone, Burch, Peter M., Landgraf, Bryan E., Segal, Rita, Lobell, Robert
Zdroj: Blood; November 1997, Vol. 90 Issue: 10 p3874-3883, 10p
Abstrakt: The native form of soluble c-kit ligand (KL) is a noncovalent dimer. We have isolated a soluble, disulfide-linked dimer of murine KL (KL-CD) by expressing KL in Escherichia coli and refolding the denatured protein under conditions that promote the formation of both noncovalent dimers (KL-NC) and KL-CD. KL-CD exhibits a 10- to 15-fold increase in the ability to stimulate the growth of both the human megakaryocytic cell line MO7e and murine bone marrow-derived mast cells relative to KL-NC. Colony-forming assays of murine bone marrow progenitor cells also reflected this increased potency. However, KL-CD and KL-NC are equally able to prime mast cells for enhanced IgE-dependent degranulation in vitro and activate mast cells in vivo. Improving the growth-promoting activity of KL without changing its mast cell activation potential suggests that KL-CD or a related molecule could be administered in the clinic at doses that stimulate hematopoietic recovery while avoiding significant mast cell activation.
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