Role of the IgE-Mediated System in Eosinophil Recruitment Triggered by Two Consecutive Cycles of Sensitisation and Challenge in Rats

Abstract

In this study, we postulated that repeated cycles of IgE passive sensitisation and antigen challenge may play a role in up-regulating eosinophil response in allergic conditions. Antigen-mediated stimulation of the pleural cavity of rats passively sensitised with a single injection of IgE anti-DNP resulted in mast cell degranulation, increase in vascular permeability and mild neutrophilia, but no pleural eosinophilia. In contrast, a second cycle of sensitisation and challenge, performed within 7 days, showed a marked eosinophilia in parallel with a lower plasma leakage and comparable neutrophilia. The eosinophilic phenomenon was not reproduced when (1) IgE sensitisation or antigen challenge was omitted in the first cycle, or (2) the first cycle was replaced by either a histamine and 5-HT dual challenge or a PAF challenge. Furthermore, we found an increase in eotaxin levels in animals subjected to two rather than one cycle of sensitisation and challenge. Treatment with the PAF receptor antagonist BN 52021 or with the lipoxygenase inhibitor zileuton, but not mast cell granule depletion, prevented the allergen-evoked eosinophil accumulation in rechallenged animals. Our results indicate that repeated cycles of IgE-driven inflammation may lead to eosinophil accumulation in a mechanism dependent on eotaxin, PAF and leukotrienes.

Long-term exacerbation by interleukin 13 of IgE-mediated eosinophilia in rats

“…Confirming previous reports [18,19], it is shown here that the hypersensitivity reaction in IgE-passively sensitized rats is insufficient to induce eosinophil recruitment (Fig. 1A).…”

“…However, studies using IgE knockout mice [13,14], B-cell deficient mice [15] and mast cell deficient mice [16] revealed that allergen-induced eosinophilic airway inflammation can occur in the absence of activation of the IgE-mast cell system. It has also been shown that a single cycle of IgE passive sensitization and challenge induced intense plasma leakage in mice [17] and rats [18,19] but failed to evoke eosinophil recruitment. Interestingly, we found a selective exacerbation of the eosinophilc response when, sites which had recovered from the first antigenic provocation, were re-stimulated within 7 days [19].…”

“…It has also been shown that a single cycle of IgE passive sensitization and challenge induced intense plasma leakage in mice [17] and rats [18,19] but failed to evoke eosinophil recruitment. Interestingly, we found a selective exacerbation of the eosinophilc response when, sites which had recovered from the first antigenic provocation, were re-stimulated within 7 days [19]. Since interleukin (IL)-13 is widely regarded as a key mediator in eosinophilic responses associated with mast cells and IgE [20][21][22], we investigated here whether IL-13 could replace the first cycle of sensitization and challenge in its proeosinophilic priming effect.…”

Pulmonary Mast Cells

“…Patients with asthma who were treated with Montelukast, which inhibits leukotrienes, a major mast cell product, demonstrated a decrease in eosinophil counts in sputum, indicating the involvement of mast cells in eosinophilia (Pizzichini et al, 1999). Furthermore, IgE-mediated degranulation of mast cells, following multiple cycles of sensitization and challenge in rats, has been shown to increase numbers of eosinophils associated with elevated eotaxin and leukotrienes, suggesting a mast cell-mediated mechanism of eosinophilic recruitment (Calheiros et al, 2001).…”

Evidence for eosinophil recruitment, leukotriene B4 production and mast cell hyperplasia following Toxocara canis infection in rats

“…Leukotriene B 4 (LTB 4 ) was originally discovered as an arachidonate metabolite that stimulates neutrophils (14), and has been described to be a chemoattractant for eosinophils (15,16). It has been shown that IgE-driven inflammation may lead to eosinophil accumulation through a mechanism dependent on eotaxin, platelet-activating factor and LTs (17). Moreover, it has been shown that eosinophil migration to the rat peritoneal cavity is mediated by mast cells, which release chemotactic factors such as LTB 4 after stimulation (18).…”