Possible Role for Platelet-Activating Factor in Neutrophil Infiltration in Allergic Inflammation in Rats

Abstract

Allergic inflammation was induced by injecting an antigen solution into an air pouch made on the dorsum of immunized rats with the antigen azobenzene-arsonate-conjugated acetyl bovine serum albumin. In this model, leukocyte infiltration into the pouch fluid was prominent 4–8 h after the antigen challenge. Most of the infiltrated leukocytes were neutrophils. Administration of the platelet-activating factor (PAF) antagonists such as CV-3988 and L-652,731 into the air pouch 15 min before and at the time of the antigen challenge failed to suppress leukocyte infiltration at 8 h. However, when the PAF antagonist was injected into an air pouch 4 h after the antigen challenge, neutrophil infiltration at 8 h was suppressed in a dose-dependent manner. Combined treatment with the 5-lipoxygenase inhibitor AA861 and the PAF antagonist did not potentiate the effect of the PAF antagonist, suggesting that participation of leukotriene B₄ in neutrophil infiltration in this model is negligible. Eosinophil infiltration was very weak at 8 h, and the PAF antagonist showed no significant effect. At 8 h, the PAF level in the serum of the immunized rats was significantly higher than that of the nonimmunized rats. Intravenous administration of the PAF antagonist 15 min before the antigen challenge suppressed leukocyte infiltration more effectively than local administration into the pouch. These results indicate that PAF plays a significant role in neutrophil infiltration in allergic inflammation.

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

“…These results are in line with those in which the eosinophil recruitment triggered by allergen, in humans [23] and guinea pigs [3], was reduced by selective PAFacether antagonists. Likewise, they are also consistent with the findings of Watanabe et al [24], who detected high concentrations of PAF-acether in the serum of im munized rats.…”

Pathological Aspects of Platelet-Activating Factor (PAF)

“…It also has a role in infiltration of polymorphonuclear leukocytes (PMNs; WATANABE et al 1990). Eosinophils are claimed to playa critical role in allergy and asthma (DE MONCHY et al 1985;GLEICH and ADOLPHSON 1986).…”

Oxidized LDL-induced leukocyte/endothelium interaction in vivo involves the receptor for platelet-activating factor.

“…One well-established consequence of oxygen radical-induced lipid peroxidation under various pathological conditions is the generation of oxidized low-density lipoprotein (oxLDL) within the vessel wall 2 or even within the bloodstream. 34 In vitro and in vivo experiments have demonstrated that oxLDL induces the chemotactic accumulation and adhesion of leukocytes to endothelial cells. 58 Both the peroxidative modification of LDL 910 and the stimulation of leukocyte adhesion by oxLDL 11 can be inhibited by superoxide dismutase (SOD), thus suggesting that these events involve a superoxide radical-dependent peroxidation of LDL and membrane phospholipids.…”