Granulocyte-Macrophage Colony-Stimulating Factor Drives Monosodium Urate Monohydrate Crystal-Induced Inflammatory Macrophage Differentiation and NLRP3 Inflammasome Up-Regulation in an In Vivo Mouse Model

被引：27

作者：

Shaw, Odette M. ^{[1
]}

Steiger, Stefanie ^{[1
]}

Liu, Xiao ^{[1
]}

Hamilton, John A. ^{[2
,3
]}

Harper, Jacquie L. ^{[1
]}

机构：

[1] Malaghan Inst Med Res, Wellington 6242, New Zealand

[2] Univ Melbourne, Parkville, Vic 3052, Australia

[3] Royal Melbourne Hosp, Parkville, Vic 3050, Australia

来源：

ARTHRITIS & RHEUMATOLOGY | 2014年 / 66卷 / 09期

关键词：

PERITONEAL MODEL; MONOCYTES; POLARIZATION; EXPRESSION; GOUT;

D O I：

10.1002/art.38730

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objective. To determine the role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the differentiation of inflammatory macrophages in an in vivo model of monosodium urate monohydrate (MSU) crystal-induced inflammation. Methods. C57BL/6J mice were treated with either clodronate liposomes to deplete peritoneal macrophages or GM-CSF antibody and were then challenged by intraperitoneal injection of MSU crystals. Peritoneal lavage fluid was collected, and cellular infiltration was determined by flow cytometry. Purified resident and MSU crystal-recruited monocyte/macrophages were stimulated ex vivo with MSU crystals. The interleukin-1 beta (IL-1 beta) levels in lavage fluids and ex vivo assay supernatants were measured. GM-CSF-derived and macrophage colony-stimulating factor (M-CSF)-derived macrophages were generated in vitro from bone marrow cells. Protein expression of IL-1 beta, caspase 1, NLRP3, and ASC by in vitro-and in vivo-generated monocyte/macrophages was analyzed by Western blotting. Results. Depletion of resident macrophages lowered MSU crystal-induced IL-1 beta and GM-CSF levels in vivo as well as IL-1 beta production by MSU crystal-recruited monocytes stimulated ex vivo. GM-CSF neutralization in vivo decreased MSU crystal-induced IL-1 beta levels and neutrophil infiltration. MSU crystal-recruited monocyte/macrophages from GM-CSF-neutralized mice expressed lower levels of the macro-phage marker CD115 and produced less IL-1 beta following ex vivo stimulation. These monocytes exhibited decreased expression of NLRP3, pro/active IL-1 beta, and pro/active caspase 1. In vitro-derived GM-CSF-differentiated macrophages expressed higher levels of NLRP3, pro/active IL-1 beta, and pro/active caspase 1 compared to M-CSF-differentiated macrophages. Conclusion. GM-CSF plays a key role in the differentiation of MSU crystal-recruited monocytes into proinflammatory macrophages. GM-CSF production may therefore contribute to the exacerbation of inflammation in gout.

引用

页码：2423 / 2428

页数：6

共 15 条

[1]

AGRO A, 1992, J RHEUMATOL, V19, P1065

[2]

ALVAROGRACIA JM, 1991, J IMMUNOL, V146, P3365

[3] Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior [J].

Auffray, Cedric ;

Fogg, Darin ;

Garfa, Meriem ;

Elain, Gaelle ;

Join-Lambert, Olivier ;

Kayal, Samer ;

Sarnacki, Sabine ;

Cumano, Ana ;

Lauvau, Gregoire ;

Geissmann, Frederic .

SCIENCE, 2007, 317 (5838) :666-670

[4] The phenotype of inflammatory macrophages is stimulus dependent: Implications for the nature of the inflammatory response [J].

Cook, AD ;

Braine, EL ;

Hamilton, JA .

JOURNAL OF IMMUNOLOGY, 2003, 171 (09) :4816-4823

[5] Granulocyte-macrophage colony-stimulating factor (CSF) and macrophage CSF-dependent macrophage phenotypes display differences in cytokine profiles and transcription factor activities: Implications for CSF blockade in inflammation [J].

Fleetwood, Andrew J. ;

Lawrence, Toby ;

Hamilton, John A. ;

Cook, Andrew D. .

JOURNAL OF IMMUNOLOGY, 2007, 178 (08) :5245-5252

[6] Blood monocytes consist of two principal subsets with distinct migratory properties [J].

Geissmann, F ;

Jung, S ;

Littman, DR .

IMMUNITY, 2003, 19 (01) :71-82

[7] Monocyte and macrophage heterogeneity [J].

Gordon, S ;

Taylor, PR .

NATURE REVIEWS IMMUNOLOGY, 2005, 5 (12) :953-964

[8] Control of macrophage lineage populations by CSF-1 receptor and GM-CSF in homeostasis and inflammation [J].

Lenzo, Jason C. ;

Turner, Amanda L. ;

Cook, Andrew D. ;

Vlahos, Ross ;

Anderson, Gary P. ;

Reynolds, Eric C. ;

Hamilton, John A. .

IMMUNOLOGY AND CELL BIOLOGY, 2012, 90 (04) :429-440

[9] RAPID CCL2 RELEASE BY MEMBRANE STROMAL CELLS INITIATES MONOSODIUM URATE CRYSTAL-INDUCED MONOCYTE RECRUITMENT IN A PERITONEAL MODEL OF GOUTY INFLAMMATION [J].

Liu, X. ;

Chia, E. ;

Shaw, O. M. ;

Martin, W-J. ;

Harper, J. L. .

EUROPEAN JOURNAL OF INFLAMMATION, 2012, 10 (02) :165-174

[10] Monosodium Urate Monohydrate Crystal-Recruited Noninflammatory Monocytes Differentiate Into M1-like Proinflammatory Macrophages in a Peritoneal Murine Model of Gout [J].

Martin, William John ;

Shaw, Odette ;

Liu, Xiao ;

Steiger, Stefanie ;

Harper, Jacquie L. .

ARTHRITIS AND RHEUMATISM, 2011, 63 (05) :1322-1332

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