Modulation of Mast Cell Proliferative and Inflammatory Responses by Leukotriene D4 and Stem Cell Factor Signaling Interactions

Mast cells (MCs) are important effector cells in asthma and pulmonary inflammation, and their proliferation and maturation is maintained by stem cell factor (SCF) via its receptor, c-Kit. Cysteinyl leukotrienes (cys-LTs) are potent inflammatory mediators that signal through CysLT(1)R and CysLT(2)R located on the MC surface, and they enhance MC inflammatory responses. However, it is not known if SCF and cys-LTs cross-talk and influence MC hyperplasia and activation in inflammation. Here, we report the concerted effort of the growth factor SCF and the inflammatory mediator LTD4 in MC activation. Stimulation of MCs by LTD4 in the presence of SCF enhances c-Kit-mediated proliferative responses. Similarly, SCF synergistically enhances LTD4-induced calcium, c-fos expression and phosphorylation, as well as MIP1 generation in MCs. These findings suggest that integration of SCF and LTD4 signals may contribute to MC hyperplasia and hyper-reactivity during airway hyper-response and inflammation. J. Cell. Physiol. 230: 595-602, 2015. (c) 2014 Wiley Periodicals, Inc., A Wiley Company