Faleiros Rafael R, Leise Britta S, Watts Mauria, Johnson Philip J, Black Samuel J, Belknap James K
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, 440 VMAB, 1900 Coffey Rd., Columbus, OH 43210, USA.
Vet Immunol Immunopathol. 2011 Nov 15;144(1-2):45-51. doi: 10.1016/j.vetimm.2011.07.005. Epub 2011 Jul 28.
Chemokines play a vital role in leukocyte activation and emigration that reportedly plays a central role in laminar injury in equine laminitis. The purpose of this study was to evaluate the pattern of laminar chemokine expression in horses in the classical carbohydrate overload (CHO)-model of laminitis. Laminar samples were obtained 24h following water administration in the control group (CON, n=8), and at the onset of fever (≥ 102°F, 12-22 h post CHO, DEV group, n=8) and at the onset of lameness (20-48 h post CHO, LAM group, n=8) in induced horses. Real time quantitative PCR was performed on all samples in order to determine laminar mRNA concentrations of both CXC chemokines (CXCL1, CXCL6, CXCL8) and CC chemokines (CCL2 [MCP-1], CCL3 [MIP-1α], and CCL8 [MCP-2]). Data were subjected to ANOVA followed by Student-Newman-Keuls (P<0.05). Laminar mRNA concentrations for all CXC chemokines were increased (P<0.05) at both the DEV and LAM horses when compared to the control horses, whereas mRNA concentrations of CCL2 and CCL8 were only increased in the LAM horses when compared to controls and the DEV horses. When taken in context with our previous studies, CXCL1, CXCL6 and CXCL8 increases precede peak laminar leukocyte accumulation. Additionally, CCL2 and CCL8 expression corroborate previous reports of monocyte/macrophage accumulation in affected laminae. Compared with previous studies, our findings demonstrate that increased laminar CXC chemokine expression consistently precedes peak leukocyte accumulation and onset of lameness in CHO laminitis models. Chemokine antagonists may be considered as possible therapeutic targets to decrease the influx of leukocytes that occurs during the development of equine laminitis.
趋化因子在白细胞激活和迁移中起着至关重要的作用，据报道，其在马属动物蹄叶炎的层状损伤中起核心作用。本研究的目的是评估在经典的碳水化合物过载（CHO）诱导的蹄叶炎模型中，马的蹄叶趋化因子表达模式。在对照组（CON，n = 8）给予水24小时后，以及在诱导的马匹发热开始时（≥102°F，CHO后12 - 22小时，DEV组，n = 8）和跛行开始时（CHO后20 - 48小时，LAM组，n = 8）采集蹄叶样本。对所有样本进行实时定量PCR，以确定CXC趋化因子（CXCL1、CXCL6、CXCL8）和CC趋化因子（CCL2 [MCP - 1]、CCL3 [MIP - 1α]和CCL8 [MCP - 2]）的蹄叶mRNA浓度。数据进行方差分析，随后进行Student - Newman - Keuls检验（P < 0.05）。与对照马相比，DEV组和LAM组马的所有CXC趋化因子的蹄叶mRNA浓度均升高（P < 0.05），而与对照组和DEV组马相比，CCL2和CCL8的mRNA浓度仅在LAM组马中升高。结合我们之前的研究，CXCL1、CXCL6和CXCL8的增加先于蹄叶白细胞积累峰值。此外，CCL2和CCL8的表达证实了先前关于受影响蹄叶中单核细胞/巨噬细胞积累的报道。与之前的研究相比，我们的研究结果表明，在CHO诱导的蹄叶炎模型中，蹄叶CXC趋化因子表达的增加始终先于白细胞积累峰值和跛行的发生。趋化因子拮抗剂可能被视为减少马属动物蹄叶炎发展过程中白细胞流入的潜在治疗靶点。
