Joubert Philippe, Cordeau Marie-Eve, Lavoie Jean-Pierre
Département de Sciences Cliniques, Faculté de Médecine Vétérinaire, Université de Montréal, St-Hyacinthe, QC, Canada.
Vet Immunol Immunopathol. 2011 Aug 15;142(3-4):236-42. doi: 10.1016/j.vetimm.2011.05.022. Epub 2011 May 24.
Heaves in horses is characterized by lower airway neutrophilic inflammation, and reversible airflow obstruction. Pulmonary macrophages contribute to the inflammation observed in a number of human and animal pulmonary diseases, and it has been postulated that they are responsible for the neutrophilic inflammation present in heaves by the release of cytokines and chemokines. To test this hypothesis, the mRNA expression of TNF-α, IL-1β, IL-8, and MIP-2 by macrophages isolated from bronchoalveolar lavage cells was quantified using real-time RT-PCR in horses with heaves (n-6) and controls (n-6). Animals were studied after being pastured for 3 months to induce clinical remission of heaves, and after 24h, and 9 days of a continuous natural antigen challenge consisting of hay feeding and straw bedding. The study was performed during 2 consecutive summers, when 3 horses with heaves and 3 control horses were evaluated. As expected, airway obstruction developed with the challenge only in horses with heaves, while airway neutrophilia was observed in both groups of horses. Stabling resulted in an increased expression of IL-8/ß-actin and MIP-2/ß-actin after 24h of stabling in both groups of horses. Further analyses revealed that compared to pasture, the expression of these chemokines was significantly increased after 24h of stabling only in Year 1, while the IL-8 expression was significantly decreased at 9 days in Year 2. No significant group, time, or year differences in IL-1β/ß-actin and TNF-α/ß-actin ratio were observed. The expression of IL-1β was strongly correlated with neutrophil percentages, although at different time points in the two study-years. These results suggest that alveolar macrophages can contribute to the airway inflammation resulting from stabling in horses by the release of IL-8 and MIP-2, but that the release of these chemokines is unlikely to be responsible for the marked airway neutrophilia observed in heaves. The variable expression of IL-8 and MIP-2 by alveolar macrophages between the two-study years are additional novel findings highlighting the complexity of the inflammatory pathways associated with airway inflammation and the importance of evaluating concurrently horses with heaves and controls to ensure identical environmental challenges.
马匹气喘的特征是下呼吸道嗜中性粒细胞炎症和可逆性气流阻塞。肺巨噬细胞在许多人类和动物肺部疾病中所观察到的炎症中发挥作用，据推测，它们通过释放细胞因子和趋化因子导致马匹气喘中存在的嗜中性粒细胞炎症。为了验证这一假设，使用实时逆转录聚合酶链反应（RT-PCR）对从患有气喘的马匹（n = 6）和对照马匹（n = 6）的支气管肺泡灌洗细胞中分离出的巨噬细胞的TNF-α、IL-1β、IL-8和MIP-2的mRNA表达进行定量。在放牧3个月以诱导气喘临床缓解后，以及在连续24小时和9天进行由干草喂养和稻草铺垫组成的持续天然抗原刺激后，对动物进行研究。该研究在连续两个夏天进行，期间评估了3匹患有气喘的马匹和3匹对照马匹。正如预期的那样，仅在患有气喘的马匹中，刺激会导致气道阻塞，而两组马匹均观察到气道嗜中性粒细胞增多。在两组马匹中，圈养24小时后，IL-8/β-肌动蛋白和MIP-2/β-肌动蛋白的表达均增加。进一步分析表明，与放牧相比，仅在第1年圈养24小时后，这些趋化因子的表达显著增加，而在第2年9天时，IL-8表达显著降低。未观察到IL-1β/β-肌动蛋白和TNF-α/β-肌动蛋白比值在组、时间或年份上的显著差异。尽管在两个研究年份的不同时间点，IL-1β的表达与嗜中性粒细胞百分比密切相关。这些结果表明，肺泡巨噬细胞可通过释放IL-8和MIP-2导致马匹圈养引起的气道炎症，但这些趋化因子的释放不太可能是气喘中观察到的明显气道嗜中性粒细胞增多的原因。两个研究年份之间肺泡巨噬细胞对IL-8和MIP-2的表达变化是另外的新发现，突出了与气道炎症相关的炎症途径的复杂性以及同时评估患有气喘的马匹和对照马匹以确保相同环境刺激的重要性。
