Increased Growth Promoting But Not Mast Cell Degranulation Potential of a Covalent Dimer of c-Kit Ligand
Karl H. Nocka,
Beth A. Levine,
Jone-Lone Ko,
Peter M. Burch,
Bryan E. Landgraf,
Rita Segal, and
Robert Lobell
From CytoMed Inc, Cambridge, MA.
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.
Blood, Vol. 90 No. 10 (November 15), 1997:
pp. 3874-3883
© 1997 by The American Society of Hematology.
