Macrophage Derived Platelet Activating Factor Implicated in the Resolution Phase of Gouty Inflammation

Abstract

Human blood derivedin vitrodifferentiated monocytes or macrophages are a population of cells which have been investigated over the years to determine the role these cells play in the resolution phase of gout. Macrophages are able to phagocytose monosodium urate monohydrate (MSU) crystals without releasing inflammatory factors. This study analysed macrophage platelet activating factor secretion and its possible role in the pathway of gout resolution. Analysis of sunatants fromin vitrodifferentiated macrophages stimulated with MSU crystals revealed the secretion of platelet activating factor (PAF)  1.54±0.10mean ± SEM; ng/mL per 106cells. This secretion was absent in immature monocytes treated similarly. When these monocytes were pretreated with recombinant human PAF-acetylhydrolase (rhuPAF-AH) and MSU crystals resulted in TNFαsuppression. Addition of WEB2086, a platelet activating factor (PAF) antagonist, to differentiated macrophages with MSU crystals unmasked TNFαsecretion0.7±0.06mean ± SEM; ng/mL per 106cells. This study identifies a role for PAF and the PAF receptor antagonist in the pathway by which macrophages ingest MSU crystals and resolve the concomitant inflammation.