Regulation Of Cytokine Gene Expression In Mast Cells

Niaid Extramural Activities

Investigators

Linked publications & trials

Abstract

Mast cells and basophils are the critical effector cells in the induction of allergic inflammation. We and others have characterized IL-4 production by human basophils and examined stimuli that regulate IL-4 synthesis and release. To relate basophil IL-4 production to environmental stimuli, we examined the ability of diesel exhuast particles (DEP) to influence this process, as DEP have been related to allergic diseases through epidemiologic studies and have been shown to participate in the development of allergic airway inflammation. DEP extract (DEPex) did induce basophil IL-4 expression in both allergic and non-allergic subjects, and this effect persisted over 20 hours. The generation of reactive oxygen species was required for the effects observed. Stem cell factor (SCF), the principal growth factor for human mast cells, is also a known chemotactic factor for these cells. Kit, the receptor for SCF, has been shown to exhibit activating mutations in cells from patients with mastocytosis. We thus hypothesized that these mutations would enhance chemotaxis. Mast cell precursors with activating mutations in Kit did migrate towards SCF to a greater degree, offering one explaination for the localized increase in mast cells in tissues of patients with mastocytosis.