IDENTIFICATION AND CHARACTERIZATION OF A SOLUBLE C-KIT RECEPTOR PRODUCED BY HUMAN HEMATOPOIETIC-CELL LINES

Stem cell factor (SCF) triggers cell growth by binding to cell surface c-kit receptors. Soluble forms of several cytokine receptors have bee n described and may play a role in the modulation of cytokine activity in vivo. For these reasons, we investigated whether human hematopoiet ic cells produce soluble c-kit receptors. The human leukemia cell line s OCIM1 and MO7e display similar to 80,000 and similar to 35,000 high- affinity cell surface c-kit receptors, respectively. Soluble c-kit rec eptors were detected by enzyme immunoassay in OCIM1 and MO7e culture s upernatants. We determined the molecular weight and binding affinity o f soluble c-kif receptor produced by OCIM1 cells, soluble c-kif recept or purified from human serum, and recombinant soluble c-kif receptor e xpressed in CHO cells. The three soluble c-kif receptors each have a m olecular weight of 98 kD. Quantitative binding experiments with I-125- SCF indicate that the soluble c-kit receptors obtained from human seru m or OCIM1 cells have binding affinities for SCF of similar to 200 to 300 pmol/L, in contrast to the recombinant form, which has a binding a ffinity of similar to 1.5 nmol/L. All three forms of the soluble c-kif receptor were able to compete with c-kif receptors on OCIM1 cells for I-125-SCF binding. Thus human hematopoietic cells can produce a solub le form of the c-kit receptor that retains high-affinity SCF binding a ctivity. We speculate that the soluble c-kif receptor may bind SCF and function as a receptor antagonist in vivo. (C) 1995 by The American S ociety of Hematology.