IgE by Itself Affects Mature Rat Mast Cell Preformed and De Novo-Synthesized Mediator Release and Amplifies Mast Cell Migratory Response

Abstract

BackgroundImmunoglobulin E (IgE) binds to high affinity receptor FcεRI numerously expressed on mast cells. Recent findings have revealed that IgE by itself may regulate various aspects of mast cell biology, however, detailed data is still limited.Methodology/FindingsHere, we have examined the influence of IgE alone, used at different concentrations, on mast cell activity and releasability. For the study we have employed in vivo differentiated mature tissue mast cells isolated from rat peritoneal cavity. Mast cells were exposed to IgE alone and then the release of preformed and de novo-synthesized mediators, surface FcεRI expression and mast cell migratory response were assessed. IgE by itself was found to up-regulate FcεRI expression and activate mast cells to degranulation, as well as de novo synthesis and release of cysteinyl leukotrienes and TNF. We have provided evidence that IgE alone also amplified spontaneous and CCL5- or TNF-induced migration of mast cells. Importantly, IgE was effective only at concentrations ≥ 3 µg/mL. A molecular basis investigation using an array of specific inhibitors showed that Src kinases, PLC/PLA2, MAP kinases (ERK and p38) and PI3K were entirely or partially involved in IgE-induced mast cell response. Furthermore, IgE alone stimulated the phosphorylation of MAP kinases and PI3K in rat mast cells.ConclusionOur results clearly demonstrated that IgE by itself, at higher concentrations, influences mast cell activity and releasability. As there are different conditions when the IgE level is raised it might be supposed that in vivo IgE is one of the important factors modulating mast cell biology within tissues.

Leptin stimulates tissue rat mast cell pro-inflammatory activity and migratory response

“…The mast cell migratory response to leptin was determined using Boyden microchamber assay in a 48-well chemotaxis chamber as previously described [ 23 ]. In brief, 30 µl of leptin (final concentrations from 0.001 to 50 ng/ml), TNF (at final concentrations of 0.01, 0.05, or 0.1 pg/ml; positive control), or buffer alone (control spontaneous migration) was placed into the lower compartments of the microchamber, which were covered with a polycarbonate 8-µm-pore-size membrane.…”

Mast cells participate in chronic low‐grade inflammation within adipose tissue

“…Finally, it should be emphasized that mast cells express integrins, cell adhesion molecules, which are involved in mast cell migration to the tissues during inflammatory processes . As mast cells express many different receptors, various endogenous and exogenous factors may activate these cells to mediator/cytokine generation and release .…”

Mannan activates tissue native and IgE-sensitized mast cells to proinflammatory response and chemotaxis in TLR4-dependent manner

“…45 Additionally, IgE binding to Fc RI enhances mast cell functional response to activation by certain agents, such as compound 48/80 and substance P. 46 We previously stated that spontaneous as well as CCL5-and TNF-induced migration of IgE-coated mast cells was significantly higher than the migration of native mast cells. 47 Interestingly, a recent report also documented that mast cell sensitization with IgE increases the expression level of microRNA-210. 48 There are also some data indicating that IgE sensitization affects mast cell response mediated by TLRs.…”