Tumes Damon J, Cormie James, Calvert Michael G, Stewart Kalev, Nassenstein Christina, Braun Armin, Foster Paul S, Dent Lindsay A
School of Molecular and Biomedical Science, University of Adelaide, North Tce, Adelaide, South Australia, Australia.
J Leukoc Biol. 2007 Jun;81(6):1362-73. doi: 10.1189/jlb.0106046. Epub 2007 Mar 22.
Although exposed to similar allergic and environmental stimuli, not all humans develop asthma. Similarly, mouse strains vary in the degree of pathophysiology seen following induction of experimental asthma. Three mouse strains (CBA/Ca, BALB/c, and C57BL/6) were used to determine if the extent and duration of inflammation influenced the degree of lung tissue damage in an OVA-induced allergic asthma model. Airways obstruction, leukocyte infiltration, edema, eosinophil accumulation, and degranulation were less severe in wild-type (wt) CBA/Ca mice than wt BALB/c and C57BL/6 mice. F1 hybrids of CBA/Ca mice crossed with BALB/c or C57BL/6 mice had bronchoalveolar lavage leukocyte (BAL) and cell-free protein profiles similar to those of the respective disease-susceptible parental strain. IL-5 transgene expression on each of the three genetic backgrounds accentuated the difference between CBA/Ca and the other two strains. Importantly, even when overexpressing IL-5, CBA/Ca mice did not develop substantial airways obstruction. Eosinophils recovered from the airways of allergic wt and IL-5 transgenic (Tg) CBA/Ca mice entered apoptosis at a faster rate than eosinophils from the other parental strains and F1 hybrids. In contrast, eosinophils harvested from the peritoneal cavities of untreated CBA/Ca IL-5 Tg mice had a relatively low rate of apoptosis in vitro. The CBA/Ca mouse strain is therefore relatively resistant to experimental asthma, and this may be a consequence of a propensity for apoptosis of eosinophils recruited into the allergic lung. Restricting survival of a key effector cell may thus limit pathogenesis in this experimental model and in humans.
尽管暴露于相似的过敏和环境刺激下，但并非所有人类都会患哮喘。同样，在实验性哮喘诱导后，不同品系的小鼠在病理生理学程度上也存在差异。使用三种小鼠品系（CBA/Ca、BALB/c和C57BL/6）来确定在卵清蛋白诱导的过敏性哮喘模型中，炎症的程度和持续时间是否会影响肺组织损伤的程度。野生型（wt）CBA/Ca小鼠的气道阻塞、白细胞浸润、水肿、嗜酸性粒细胞积聚和脱颗粒情况比wt BALB/c和C57BL/6小鼠轻。CBA/Ca小鼠与BALB/c或C57BL/6小鼠杂交产生的F1杂种的支气管肺泡灌洗白细胞（BAL）和无细胞蛋白谱与各自疾病易感亲本品系相似。在三种遗传背景下的白细胞介素-5转基因表达加剧了CBA/Ca与其他两种品系之间的差异。重要的是，即使过度表达白细胞介素-5，CBA/Ca小鼠也不会出现严重的气道阻塞。从过敏性wt和白细胞介素-5转基因（Tg）CBA/Ca小鼠气道中回收的嗜酸性粒细胞比来自其他亲本品系和F1杂种的嗜酸性粒细胞更快地进入凋亡。相比之下，从未经处理的CBA/Ca白细胞介素-5 Tg小鼠腹腔中收获的嗜酸性粒细胞在体外的凋亡率相对较低。因此，CBA/Ca小鼠品系对实验性哮喘相对具有抗性，这可能是招募到过敏性肺中的嗜酸性粒细胞易于凋亡的结果。因此，限制关键效应细胞的存活可能会限制该实验模型和人类中的发病机制。
