Role of PAF in the allergic pleurisy caused by ovalbumin in actively sensitized rats

Abstract

Selective platelet-activating factor (PAF) antagonists and autodesensitization to this lipid were used to investigate the role of PAF in antigen-induced pleurisy in the rat. Pleural inflammation was triggered by the intrathoracic (i.t.) injection of ovalbumin (12 micrograms/cavity) into animals actively sensitized 14 days before. Successive daily i.t. injections of PAF (1 microgram/cavity) led to selective autodesensitization, which was apparent after the third injection and maximal after the fifth. The PAF antagonists BN 52021 and WEB 2086 inhibited the late pleural eosinophil accumulation caused by antigen but, as also noted with WEB 2170, failed to modify the early antigen-induced plasma exudation and leukocyte infiltration. In contrast to the antagonists, desensitization to PAF was clearly effective against these early alterations. To further investigate this discrepancy, the antigenic challenge was performed 24 h after a single prestimulation with PAF, when sensitivity to the lipid was still intact. Under this condition, plasma exudation and cellular influx triggered by the antigen were also abrogated, indicating that this protective effect was accounted for by a mechanism other than refractoriness to PAF. Because 24 h after PAF injection only eosinophil counts remained elevated, an alternative eosinophilotactic substance was used to further study the mechanism of PAF versus antigen-induced pleural inflammation. Prior treatment with the peptide Ala-Gly-Ser-Glu (ECF-A, 20 micrograms/cavity) also inhibited the allergic pleurisy, whereas the noneosinophilotactic substances histamine (200 micrograms/cavity) and serotonin (100 micrograms/cavity) were inactive. Furthermore, drugs that share the ability to impair PAF-induced eosinophilia, including azelastine and cetirizine, prevented the inhibitory effect of PAF on the antigen-induced pleurisy. These findings suggest that PAF may account for the late eosinophilia, but not for the acute phase of the rat allergic pleurisy, which is clearly attenuated by PAF or ECF-A pretreatment.

Aqueous extract of Bowdichia virgilioides stem bark inhibition of allergic inflammation in mice

“…According to previously published data, OVA challenge induced a marked increase in total leukocyte numbers in the pleural cavity within 24 h, with a significant accumulation of eosinophils (Martins et al, 1993). Based on that data, we examined leukocyte influx into the pleura cavity, and our results show that AEBv treatment attenuated polymorphonuclear accumulation, mainly eosinophils influx, in the allergic pleurisy without a significant change in mononuclear cell recruitment.…”

“…Allergic pleurisy was performed as described by Martins et al (1993) with modifications. Mice were actively sensitized by dorsal subcutaneous injection of a mixture containing 50 mg OVA and 5 mg aluminum hydroxide in a final mixture volume of 0.2 mL.…”

A Novel Effect for Annexin 1-Derived Peptide Ac2-26: Reduction of Allergic Inflammation in the Rat

“…These changes are followed by neutrophil influx, peaking from 4 to 8 h, and mononuclear cell and eosinophil influx, first noted at 8 h but peaking from 12 to 24 h postallergen challenge (Lima et al, 1997). All these events were clearly sensitive to the systemic treatment with dexamethasone, whereas histamine and 5-hydroxytryptamine receptor antagonists inhibited plasma leakage without altering leukocyte infiltration (Martins et al, 1993). In our first set of experiments, we have shown that the local administration of peptide Ac2-26 reduced plasma leakage and neutrophil and eosinophil emigration into the rat pleural space, leaving intact the mononuclear cell enrichment caused by allergen challenge.…”

Pharmacological study of anti-allergic activity of Syzygium cumini (L.) Skeels

“…Supporting these observations, treatment with SC displayed an inhibitory effect on edema induced by histamine and 5-HT, but failed to inhibit PAF-induced paw edema. The participation of PAF in edema forma- tion and eosinophil mobilization in allergic inflammation has been reported (20,21) and the lack of effect of the SC extract on PAFinduced edema and the participation of the other mediators in the triggering of allergic paw edema may account for discrete effect of the SC extract on allergic paw edema. These results suggest that the SC extract can be much more effective in inhibiting reactions whose mechanism depends on the release of histamine and of 5-HT.…”