Antiinflammatory activity of the platelet-activating factor receptor antagonist A-85783

Abstract

Accumulating evidence suggests an important role for the lipid mediator, platelet-activating factor (PAF), in cutaneous inflammation. In these studies the antiinflammatory effects of the potent and selective lipophilic PAF receptor antagonist A-85783 topically applied to the ventral ears of male Wistar rats were assessed. Intradermal injections of PAF into rat ears resulted in cutaneous inflammation as assessed by both ear thickness measurements and histological evaluation. Pretreatment of the ears with A-85783 resulted in an inhibition of subsequent PAF-induced inflammation. A-85783 treatment also inhibited phorbol myristic acetate-induced cutaneous inflammation, suggesting that the PAF receptor is involved in the etiology of this experimental dermatitis. These findings demonstrate that epicutaneous A-85783 is an appropriate tool to study the role of the PAF receptor in cutaneous inflammation, and suggest the possible clinical utility of this new class of antiinflammatory agents.

Thermal Burn Injury Generates Bioactive Microvesicles: Evidence for a Novel Transport Mechanism for the Lipid Mediator Platelet-Activating Factor (PAF) That Involves Subcellular Particles and the PAF Receptor

“…The PAF lipids are preserved in the MVP, whereas acetylhydrolases in the cell remove the cellular PAF. Finally, to confirm the PAFR biological activity of MVP, we took advantage of the known ability of PAF to generate acute skin inflammation in a process because of PAFRdependent mast cell degranulation (49,50). To test this, we topically treated the dorsal ears of wild-type and PAFR-deficient mice with lipid extracts from MVP derived from either untreated or thermal burn injury-treated HaCaT cells and measured ear thickness using calipers.…”

Staphylococcal lipoteichoic acid inhibits delayed-type hypersensitivity reactions via the platelet-activating factor receptor

“…After 2 hours, 5-mm punch biopsy samples were taken from the ears, and inflammation was assessed by weighing the specimens. The 2-hour period was chosen as this is the time of maximal inflammation (as measured by tissue weight) we have previously determined for intradermal injection of CPAF in rats (25). As shown in Figure 2, A and B, both wild-type and PAF-R -/-mice were equally responsive to the positive control, intradermal injection of histamine.…”

New Insights Into the Pathologic Roles of the Platelet-Activating Factor System

“…Moreover, PAF can be detected in cold urticaria (119), immunobullous diseases such as bullous pemphigoid (120), following sunburn (121), and in the skin disease psoriasis (122). Consistent with the notion that PAF could exert cutaneous effects, intradermal injection or topical application of PAF onto skin results in an almost immediate painful urticarial response (68)(69)(70)(71).…”