Rat mast cell activation and inactivation: Differences when various ligands are used to induce secretion

Abstract

The relationship between rat peritoneal mast cell activation and inactivation (desensitization) was studied for a variety of stimuli acting via IgE and IgG receptors on the cell surface. Anti-IgE, antigen (ovalbumin), anti-IgG1, anti-IgG2a and dimers, trimers and higher oligomers of IgE were used to induce histamine release from rat mast cells. All produced similar characteristics of cell activation, with a rapid rate of histamine release from the cells, release being 90% complete within 5 minutes and with calculated doubling times between 21.6 +/- 3.6 s (+/- SEM) for ovalbumin and 93.0 +/- 18.6 s (+/- SEM) for anti-IgG1. The characteristics of inactivation, however, varied with the releasing agent used. Of all the stimuli used only ovalbumin showed a rapid rate of desensitization (t 1/2 = 330 +/- 34.8 s) which correlated with the cessation of histamine release. The other stimuli showed slow rates of desensitization (t 1/2 between 1068 +/- 40.2 s for dimer and 3576 +/- 660 s for anti-IgE) even though the rate of release was rapid. Thus, although these stimuli are thought to be stimulating the cells by cross-linking of either IgE or IgG receptors, the difference in subsequent response of the cells would indicate that the transduction mechanism bringing about release can distinguish between these various stimuli. Also, it seems that the idea that duration of histamine release is determined by the rate of desensitization may need revising as with most of these stimuli, release has terminated when the cells are still in a fully activated state.

Lysophosphatidic acid triggers mast cell-driven atherosclerotic plaque destabilization by increasing vascular inflammation

“…For total (100%) release measurements, mast cells were lysed with 10% Triton X-100 and untreated control cell supernatant served as 0% release control. In vivo mast cell activation was determined in C57Bl/6 mice and mast cell defi cient Kit(W Ϫ sh /W Ϫ sh ) mice that had received intraperitoneal IgE receptor by multiple IgE molecules ( 8 ), neurogenic stimulation ( 8,9 ), infl ammatory stimuli (e.g., tumor necrosis factor ␣ and IL-1), and complement factors (e.g., C3a and C5a) ( 10 ). Although the endogenous triggers for mast cell activation in atherosclerosis are still unknown, IgE ( 11 ), IgG-oxidized low-density lipoprotein (oxLDL) immune complexes ( 12 ), the neuropeptide substance P ( 9,13 ), and the complement system ( 14 ) were suggested to activate mast cells in atherosclerosis.…”

In contrast to specific B cells, human basophils are unaffected by the toxic activity of an allergen toxin due to lack of internalization of immunoglobulin E‐bound allergen

“…Considering the unexpected results, other experiments concerning cross-linking and internalization which were almost all performed with RBL-cells and/or a monomeric loading with IgE should probably be repeated with ex vivo cells. It seems that there are indeed differences between the stimulation of ex vivo mast cells with allergen, anti-IgE or IgE-dimer [29,30]. The resistance of basophils to the AT was quite unexpected after the results for the hybridoma cell lines.…”