Pharmacological Modulation of the Late Eosinophilia Induced by Antigen in Actively Sensitized Rats

Abstract

The intrathoracic injection of ovalbumin (12 μg/cavity) into actively sensitized rats led to a long-lasting eosinophil recruitment, which appeared 24 h after stimulation. In this study, pharmacological antagonists were used in order to evaluate the potential involvement of arachidonic acid metabolites and PAF-acether in the pleural eosinophil accumulation by antigen. Administration of the cyclooxygenase inhibitor indomethacin (2 mg/kg, i.p.), 1 h before the antigen challenge, failed to modify the 24-hour eosinophilia. In contrast, the dual cyclooxygenase and lipoxygenase inhibitor BW 755C and the more selective inhibitor BW A4C (5 and 10 μg/cavity, i.t.), injected 1 h before the antigen, were effective. Similarly, the PAF-acether antagonists BN 52021 and WEB 2086 (20 mg/kg, i.p.) abrogated the eosinophil accumulation, which was also sensitive to the topical treatment with the glucocorticoid dexamethasone (5 and 10 μg/ cavity). Our findings suggest that the antigen-induced eosinophil mobilization is dependent on lipoxygenase derivatives and PAF-acether, but not on prostaglandins.

Mast cell changes in experimental diabetes: focus on attenuation of allergic events

“…In accordance with the above observation, using the model of pleural allergic response in rats (Lima et al 1990, 1991, Silva et al 1992, we found that sensitized animals rendered diabetic after alloxan reacted to antigenic challenge with 50% reduction in the number of eosinophils recruited to the pleural cavity (Diaz et al 1996(Diaz et al , 1997. The less pronounced eosinophil accumulation did not relate to an intrinsic cell locomotor abnormality since eosinophils from diabetic rats presented similar chemotactic responses in vitro as compared to matching controls (Diaz et al 1996).…”

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

“…Our results demonstrate that the anti-PAF receptor antagonist BN52021 and 5-lipoxygenase inhibitor zileuton abolished the eosinophilia triggered after antigen re-exposure, strongly suggesting the contribution of PAF and 5-lipoxygenase derivatives as eosinophil chemoattractants in this model. Similarly, Silva et al [51]have shown that PAF antagonists and lipoxygenase inhibitor were able to inhibit antigen-induced pleural eosinophilia in actively sensitised rats. Our results also revealed that the peptide bradykinin does not appear to be involved in the current model of pleural eosinophilia, since pretreatment with the B 2 receptor antagonist Hoe 140 did not modify the number of these cells after rechallenge.…”

Antigen-induced pleural eosinophilia is suppressed in diabetic rats: role of corticosteroid hormones

“…injection of OVA (12 µg/cavity). Pleurisy was evaluated as previously described (Silva et al 1992). Total and differential leucocyte counts were performed in an automatic cell counter and in cytospin preparations stained with May-GrunwaldGiemsa dye, respectively.…”