The 12th World Congress on Inflammation

Yagnik, Darshna (2015) The 12th World Congress on Inflammation. Inflammation Research, 64 (S2) . pp. 51-248. ISSN 1023-3830 [Article] (doi:10.1007/s00011-015-0839-4)


Background: A model of gout which consists of human blood derived in vitro differentiated monocytes/macrophages and neutrophils are immune cells which have been investigated over the years to determine the role these cells play in the resolution phase of gout. Macrophages and neutrophils are able to phagocytose monosodium urate monohydrate (MSU) crystals without releasing inflammatory factors. This study analysed platelet activating acetylhydrolase (PAFAH) secretion by human macrophages and neutrophils derived from whole blood upon phagocytosis of MSU crystals.
Method: Monocytes and neutrophils were isolated from whole blood taken from human blood donations collected from the National Blood NHS Service using standard isolation procedures using percoll and dextran sedimentation. Isolated monocytes were differentiated for a period of 7 days in vitro into macrophages. Day 1 monocytes or day 7 in vitro differentiated macrophages were then stimulated with MSU crystals (0.5 mg/mL), or LPS (10 lg/mL) and signalling inhibitors for a period of 17 h. Cultured supernatants were then collected and assayed for Tumour necrosis (TNF) alpha, PAF acetyl hydrolase (PAF-AH) secretion by ELISA.
Results: Analysis of supernatants from in vitro differentiated macrophages stimulated with MSU crystals revealedPAF-AH secretion whereas monocytes did not secreted PAF-AH. Release of macrophage PAF-AH (0.6 pg/mL ± 0.01) was inhibited by a protein kinase inhibitor (SB203580 at a range of 50–300 nM) when added to the assay at the same time as MSU crystals. Similar results were obtained with neutrophils.
Conclusion: This study identifies a role for neutrophil and macrophage derived PAF-AH in inflammation resolution through PKC signalling in the pathway by which immune cells ingest MSU crystals and resolve the concomitant inflammation. The PAF-AH enzyme could be used therapeutically for treatment of patients with recurrent or treatment resistant gout.

Item Type: Article
Research Areas: A. > School of Science and Technology > Natural Sciences > Biomarkers for Cancer group
Item ID: 22048
Depositing User: Darshna Yagnik
Date Deposited: 19 Jun 2017 08:51
Last Modified: 19 Jun 2017 08:51

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