Histamine 4 receptor plays an important role in auto-antibody-induced arthritis

被引:9
作者
Nent, Elisa [1 ]
Frommholz, David [1 ]
Gajda, Mieczyslaw [2 ]
Braeuer, Rolf [2 ]
Illges, Harald [1 ]
机构
[1] Univ Appl Sci, Dept Nat Sci Immunol & Cell Biol, D-53359 Rheinbach, Germany
[2] Univ Hosp Jena, Inst Pathol, Jena, Germany
关键词
autoimmune disease; histamine receptor antagonist; K/BxN model; H-4; RECEPTOR; MAST-CELLS; INFLAMMATORY ARTHRITIS; RHEUMATOID-ARTHRITIS; SYNOVIAL-CELLS; EXPRESSION; IMMUNE; AGRANULOCYTOSIS; DEFICIENCY; DISORDERS;
D O I
10.1093/intimm/dxt008
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Rheumatoid arthritis is a widespread autoimmune disease. In the murine K/BN arthritis model, anti-GPI (anti-glucose 6-phosphate isomerase) antibodies lead to the formation of immune complexes. In the course of pathogenesis, these complexes activate the immune system and induce degranulation of mast cells, which are essential in this model of rheumatoid arthritis. A major mediator in mast cell granules is histamine, which is proven to be indispensable for joint inflammation in K/BN mice. Histamine is known to bind to four different receptors (HR14), which have different expression profiles and exert a variety of different functions, including activation of the immune system. To analyze the contribution of the different histamine receptors, we employed histamine receptor antagonists (cetirizine, ranitidine, thioperamide and clozapine) blocking the receptors in C57BL/6 mice. Arthritis was induced via K/BN serum injection. The results demonstrated that mice treated with all four histamine receptor antagonists simultaneously showed no arthritic symptoms, while positive control mice injected with K/BN serum and vehicle suffered from severe symptoms. When antagonists specific for HR14 were applied individually, only the HR4 antagonist clozapine could protect mice from arthritis, reflecting its expression and functionality in the immune system.
引用
收藏
页码:437 / 443
页数:46
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