Characterization of syk expression in human lung mast cells: relationship with function

Abstract

These studies indicate that although syk may play an important role in mediating degranulation, the relative level of syk expression does not govern human lung mast cell releasability. Identification of the mechanisms that govern IgE-dependent activation of human lung mast cells is likely to be of wider clinical significance, given the central role that mast cells play in the development of allergic asthma.

IgE-dependent signaling as a therapeutic target for allergies

“…This characteristic motivated the development of syk inhibitors for both atopic and other inflammatory diseases, such as rheumatoid arthritis (RA). Effective inhibition of syk, either through genetic means in mice or pharmacological means in humans completely ablates FcεRI-mediated secretion and essentially any other pro-inflammatory function that has been studied in mast cells/basophils [9, 10]. Recent syk inhibitors show both high potency and selectivity.…”

“…It is estimated that in human basophils, there are 5–8 FcεRI molecules for each molecule of syk (25,000 syk molecules per basophils vs. 150,000 molecules of FcεRI) [29]. Mast cells express about twice as much syk as basophils but still less than most leukocytes [10]. It appears that syk expression is tuned to be just sufficient to drive the IgE-mediated reaction.…”

Heterogeneity in the responses of human lung mast cells to stem cell factor

“…Moreover, the response is not affected by purification [22]. Either anti-IgE or SCF was used to activate the cells.…”

The potential use of tyrosine kinase inhibitors in severe asthma

“…Piceatannol, a Syk TKI, inhibited histamine release and attenuated in-vitro bronchial contraction of guinea pig airway muscle [79]. Although Syk inhibition blunts histamine release, it does not seem to regulate IgE-dependent activation of mast cells [80]. In a rat model, the Syk TKI BAY 61-3606 reduced airway inflammatory cells, bronchial edema, and, possibly, improved bronchoconstriction, as measured by BALF cell analysis, Evans blue dye extravasation from cells, and airway pressures measurements, respectively [81].…”