Noninflammatory phagocytosis of monosodium urate monohydrate crystals by mouse macrophages: implications for the control of joint inflammation in gout

Yagnik, Darshna and Hillyer, Philippa and Marshall, Diane and Smythe, Cheryl D. and Krausz, Thomas and Haskard, Dorian O. and Landis, R. Clive (2000) Noninflammatory phagocytosis of monosodium urate monohydrate crystals by mouse macrophages: implications for the control of joint inflammation in gout. Arthritis and Rheumatism, 43 (8). pp. 1779-1789. ISSN 0004-3591

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Abstract

Objective
We have hypothesized that the process of monocyte to macrophage differentiation may alter the inflammatory response of mononuclear phagocytes to the uptake of monosodium urate monohydrate (MSU) crystals.
Methods
Eight mouse monocyte/macrophage cell lines were arranged in increasing order of differentiation, as judged by expression of the macrophage markers F4/80 and BM 8 and by phagocytic capacity. Secretion of tumor necrosis factor α (TNFα) in response to MSU was measured by enzyme-linked immunosorbent assay.
Results
The panel of monocyte/macrophage cell lines revealed a close linkage between the state of differentiation and the capacity of the cells to ingest MSU crystals. TNFα production, however, was not linked to phagocytic ability. Peak TNFα levels were synthesized by cells at an intermediate state of differentiation (3.2–14.1 ng/ml), whereas mature macrophages, which efficiently phagocytosed crystals, did not secrete TNFα. Mature cell lines produced TNFα when stimulated with zymosan (5.9–6.2 ng/ml), but this was abolished by coincubation with MSU crystals. Suppression of the zymosan response was not due to apoptosis or steric hindrance by MSU crystals. Culture supernatants from mature macrophages did not stimulate endothelial cell activation, in contrast to MSU-treated cells at an earlier stage of differentiation, which stimulated intercellular adhesion molecule 1 expression on sEND endothelioma cells through the release of TNFα (inhibited 80.6% by anti-TNFα).
Conclusion
We demonstrated that phagocytosis and TNFα production are distinct events in the response of mononuclear phagocytes to urate crystals, and these events can be distinguished at the level of macrophage differentiation. The noninflammatory removal of urate crystals by mature macrophages defines a new pathway that may be important in controlling the development of acute gout in patients with hyperuricemia.

Item Type: Article
Additional Information: PubMed PMID: 10943868.
Research Areas: A. > School of Science and Technology > Natural Sciences
ISI Impact: 43
Item ID: 2497
Useful Links:
Depositing User: Repository team
Date Deposited: 17 Jun 2009 11:40
Last Modified: 15 Feb 2016 15:06
URI: http://eprints.mdx.ac.uk/id/eprint/2497

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