Chapter 37 - Release and Cleavage of Stem Cell Factor by Human Mast Cells

Abstract

This chapter provides evidence that the secretory granules of cardiac mast cells (HHMC) store stem cell factor (SCF) and analyzes the potential role of chymase, a chymotrypsin-like protease, also present in the secretory granules of human mast cells, in the cleavage process of SCF. The findings lead to the suggestion that SCF, present in the secretory granules of mast cells, might represent an autocrine factor sustaining the characteristic mast cell hyperplasia in allergic patients and in patients with mastocytosis. It was also found that SCF can be immunologically released by isolated and purified mast cells, and that chymase and other proteolytic enzymes, also present in the secretory granules of human mast cells, can cleave SCF. Several species of SCF may be formed in vivo, and chymase selectively acts at Phe159 whereas other proteases may further cleave SCE. Thus, the immunological activation of human mast cells could lead to the concomitant release of SCF and of SCF-digesting proteases. These novel results highlight the complexity of the autocrine loops and negative feedbacks involving human mast cells and their metabolic products.