Lin Tzu-Yin, London Cheryl A
Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, 454 VMAB, 1925 Coffey Road, Columbus, OH 43210, USA.
Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, 454 VMAB, 1925 Coffey Road, Columbus, OH 43210, USA.
Vet Immunol Immunopathol. 2010 May 15;135(1-2):118-127. doi: 10.1016/j.vetimm.2009.11.010. Epub 2009 Nov 24.
Mast cells play an important role in both innate and acquired immunity as well as several pathological conditions including allergy, arthritis and neoplasia. They influence these processes by producing a variety of mediators including cytokines, chemokines and eicosanoids. Very little is currently known about the spectrum of inflammatory mediators, particularly eicosanoids (prostaglandins and leukotrienes), produced by canine mast cells. This is important since modulating mast cell derived eicosanoids may help in the treatment of autoimmune and inflammatory disorders. The purpose of this study was to investigate the spectrum of eicosanoids produced by normal canine mast cells and to evaluate the effects of cytokines and non-steroidal anti-inflammatory mediators (NSAIDS) on eicosanoid production and release. Canine bone marrow derived cultured mast cells (cBMCMCs) expressed COX-1, COX-2, and 5-LOX and synthesized and released PGD2, PGE2, LTB4, and LTC4 following activation by a variety of stimuli. The selective COX-2 NSAIDs carprofen (Rimadyl) and deracoxib (Deramaxx) inhibited PGD2 and PGE2 production but only slightly inhibited LTB4 and LTC4. The mixed COX-1/COX-2 inhibitor piroxicam blocked PGD2 and PGE2 production, but upregulated LTC4 following treatment while tepoxilan (Zubrin), a pan COX/LOX inhibitor, markedly reduced the production of all eicosanoids. The LOX inhibitor nordihydroguaiaretic acid (NDGA) prevented LTB4/LTC4 release and BMBMC degranulation. Pre-incubation of cBMCMCs with IL-4 and SCF sensitized these cells to degranulation in response to substance P. In conclusion, canine BMCMCs produce an array of eicosanoids similar to those produced by mast cells from other species. Tepoxilan appeared to be the most effective NSAID for blocking eicosanoid production and thus may be useful for modulating mast cell mediated responses in dogs.
肥大细胞在先天性免疫和获得性免疫以及包括过敏、关节炎和肿瘤形成在内的多种病理状况中发挥着重要作用。它们通过产生多种介质（包括细胞因子、趋化因子和类花生酸）来影响这些过程。目前对于犬肥大细胞产生的炎性介质谱，尤其是类花生酸（前列腺素和白三烯）了解甚少。这一点很重要，因为调节肥大细胞衍生的类花生酸可能有助于治疗自身免疫性和炎性疾病。本研究的目的是调查正常犬肥大细胞产生的类花生酸谱，并评估细胞因子和非甾体抗炎介质（NSAIDs）对类花生酸产生和释放的影响。犬骨髓来源的培养肥大细胞（cBMCMCs）表达COX-1、COX-2和5-LOX，并在受到多种刺激激活后合成并释放PGD2、PGE2、LTB4和LTC4。选择性COX-2 NSAIDs卡洛芬（瑞莫迪）和地拉考昔（Deramaxx）抑制PGD2和PGE2的产生，但仅轻微抑制LTB4和LTC4。COX-1/COX-2混合抑制剂吡罗昔康阻断PGD2和PGE2的产生，但在处理后上调LTC4的产生，而泛COX/LOX抑制剂替泊昔兰（祖布林）显著降低所有类花生酸的产生。LOX抑制剂去甲二氢愈创木酸（NDGA）可阻止LTB4/LTC4的释放和BMBMC的脱颗粒。用IL-4和SCF对cBMCMCs进行预孵育可使这些细胞对P物质的刺激敏感而发生脱颗粒。总之，犬BMCMCs产生一系列类似于其他物种肥大细胞产生的类花生酸。替泊昔兰似乎是阻断类花生酸产生最有效的NSAID，因此可能有助于调节犬肥大细胞介导的反应。
