5-Lipoxygenase-deficient mice infected with Borrelia burgdorferi develop persistent arthritis.
5-Lipoxygenase-deficient mice infected with Borrelia burgdorferi develop persistent arthritis.
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DOI：
10.4049/jimmunol.1003473
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发表时间：
2011-03-01
期刊：
影响因子：
--
通讯作者：
Brown CR
中科院分区：
文献类型：
--
作者：
Blaho VA;Zhang Y;Hughes-Hanks JM;Brown CR
5-脂氧合酶（5-LO）催化花生四烯酸转化为白三烯，白三烯是炎症和炎症性疾病（如哮喘和关节炎）的关键调节因子。虽然白三烯存在于莱姆病患者的滑液中，但它们在莱姆病关节炎发展中的作用尚未确定。在目前的研究中，我们使用小鼠莱姆病模型来研究5-LO产品在这种炎症性疾病的发展中可能发挥的作用。莱姆病易感C3H/HeJ小鼠感染伯氏疏螺旋体后，诱导关节内5-LO和5-脂氧合酶激活蛋白（FLAP） mRNA表达，产生5-LO产物LTB4。利用C3H 5-LO缺陷小鼠，我们证明5-LO活性不是诱导莱姆病的必要条件，但其缺乏导致早期关节肿胀和无法解决关节炎，这在感染后60天的持续关节炎病理中得到了证明。虽然5- lo缺陷小鼠抗伯氏疏螺旋体IgG的产生减少，但关节的细菌清除不受影响。5- lo缺陷小鼠巨噬细胞对伯氏螺旋体的吞噬和凋亡中性粒细胞的吞噬功能存在缺陷，中性粒细胞对活化的螺旋体的摄取减少。这些结果表明，在所有关节炎模型中，疾病的发展并不需要5-LO代谢途径的产物，因此在将5-LO作为炎症性疾病的治疗时应谨慎。
The enzyme 5-lipoxygenase (5-LO) catalyzes the conversion of arachidonic acid into the leukotrienes, which are critical regulators of inflammation and inflammatory diseases, such as asthma and arthritis. Although leukotrienes are present in the synovial fluid of Lyme disease patients, their role in the development of Lyme arthritis has not been determined. In the current study, we used a murine model of Lyme arthritis to investigate the role 5-LO products might have in the development of this inflammatory disease. Following infection of Lyme arthritis-susceptible C3H/HeJ mice with B. burgdorferi, mRNA expression of 5-LO and 5-lipoxygenase-activating protein (FLAP) was induced in the joints, and the 5-LO product LTB4 was produced. Utilizing C3H 5-LO-deficient mice, we demonstrated that 5-LO activity was not necessary for the induction of Lyme arthritis, but that its deficiency resulted in earlier joint swelling and an inability to resolve arthritis as demonstrated by sustained arthritis pathology through day 60 post-infection. Although production of anti-Borrelia IgG was decreased in 5-LO-deficient mice, bacterial clearance from the joints was unaffected. Phagocytosis of B. burgdorferi and efferocytosis of apoptotic neutrophils was defective in macrophages from 5-LO-deficient mice, and uptake of opsonized spirochetes by neutrophils was reduced. These results demonstrate that products of the 5-LO metabolic pathway are not required for the development of disease in all models of arthritis, and that caution should be used when targeting 5-LO as therapy for inflammatory diseases.
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DOI：
10.4269/ajtmh.1992.47.605
发表时间：
1992-11-01
影响因子：
3.3
作者：
BARTHOLD, SW;SIDMAN, CL;SMITH, AL
通讯作者：
SMITH, AL
影响因子：
15.3
作者：
Griffiths, R J;Smith, M A;Roach, M L;Stock, J L;Stam, E J;Milici, A J;Scampoli, D N;Eskra, J D;Byrum, R S;Koller, B H;McNeish, J D
通讯作者：
McNeish, J D
DOI：
10.1084/jem.20021183
发表时间：
2002-11-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Aliberti J;Serhan C;Sher A
通讯作者：
Sher A
影响因子：
15.9
作者：
Fadok, VA;Bratton, DL;Henson, PM
通讯作者：
Henson, PM
影响因子：
5.5
作者：
Boxio, R;Bossenmeyer-Pourié, C;Nüsse, O
通讯作者：
Nüsse, O