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Absence of a lyso-PAF relationship with PAF (platelet activating factor) in monosodium urate crystal-induced
D E Griswold1, L Hillegass, D Rotilio
1Department of Immunology, SK&F Laboratories, Swedeland, PA 19479.
Abstract:
Monosodium urate crystal (MSU)-induced inflammation was evaluated for increased vascular permeability and platelet activating factor (PAF) production. Intraperitoneal injection of MSU crystals increased vascular permeability and lyso-PAF, as shown by acetylation and bioassay, but PAF was not detected. Intraperitoneal administration of PAF elicited dye-extravasation, which was abolished by the PAF antagonist WEB-2086, but this compound had no significant effect upon MSU-induced dye extravasation. Thus, the presence of lyso-PAF did not reflect in situ production of PAF. Lyso-PAF extracted from normal serum in amounts equivalent to that extravasated could account for the lyso-PAF observed. Thin-layer chromatographic analysis of acetylated extracts from plasma and peritoneal washouts showed identical Rf values to the PAF standard. We conclude that lyso-PAF in the exudate was associated with extravasated plasma proteins rather than a reflection of in situ production of PAF.
Insights
Monosodium urate crystal (MSU) inflammation increases vascular permeability and lyso-platelet activating factor (PAF). However, the study found lyso-PAF in exudates originated from plasma, not local PAF production.
Area of Science:
- Inflammation and Immunology
- Biochemistry
- Vascular Biology
Background:
- Monosodium urate (MSU) crystals induce inflammation.
- Platelet-activating factor (PAF) is implicated in inflammatory processes.
- Vascular permeability is a key feature of inflammation.
Purpose of the Study:
- To investigate the role of PAF in MSU-induced inflammation.
- To determine if lyso-PAF detected in exudates reflects local PAF production.
- To assess the contribution of PAF to increased vascular permeability during MSU-induced inflammation.
Main Methods:
- MSU crystals were injected intraperitoneally to induce inflammation in a model.
- Vascular permeability was assessed using dye extravasation.
- Lyso-PAF and PAF levels were measured using acetylation, bioassays, and thin-layer chromatography.
- The effect of a PAF antagonist (WEB-2086) was evaluated.
Main Results:
- MSU crystal injection increased vascular permeability and lyso-PAF levels.
- PAF itself was not detected in the peritoneal exudate.
- The PAF antagonist WEB-2086 did not inhibit MSU-induced dye extravasation.
- Lyso-PAF levels in exudates were consistent with amounts found in normal serum.
Conclusions:
- The presence of lyso-PAF in MSU-induced exudates is likely due to extravasation from plasma, not de novo PAF synthesis.
- PAF does not appear to be the primary mediator of MSU-induced vascular permeability in this model.
- These findings clarify the origin of lyso-PAF in inflammatory exudates.