Oliveira S H, Faccioli L H, Ferreira S H, Cunha F Q
Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, SP, Brasil.
Mem Inst Oswaldo Cruz. 1997;92 Suppl 2:205-10. doi: 10.1590/s0074-02761997000800028.
There are several experimental models describing in vivo eosinophil (EO) migration, including ip injection of a large volume of saline (SAL) or Sephadex beads (SEP). The aim of this study was to investigate the mechanisms involved in the EO migration in these two models. Two consecutive injections of SAL given 48 hr apart, induced a selective recruitment of EO into peritoneal cavity of rats, which peaked 48 hr after the last injection. SEP, when injected ip, promoted EO accumulation in rats. The phenomenon was dose-related and peaked 48 hr after SEP injection. To investigate the mediators involved in this process we showed that BW A4C, MK 886 and dexamethasone (DXA) inhibited the EO migration induced by SAL and SEP. To investigate the source of the EO chemotactic factor we showed that mast cells, macrophages (MO), but not lymphocytes, incubated in vitro in presence of SAL released a factor which induced EO migration. With SEP, only mast cells release a factor that induced EO migration, which was inhibited by BW A4c, MK 886 and DXA. Furthermore, the chemotactic activity of SAL-stimulated mast cells was inhibited by antisera against IL-5 and IL-8 (interleukins). SAL-stimulated MO were only inhibited by anti-IL-8 antibodies as well SEP-stimulated mast cells. These results suggest that the EO migration induced by SAL may be dependent on resident mast cells and MO and mediated by LTB4, IL-5 and IL-8. SEP-induced EO migration was dependent on mast cells and may be mediated by LTB4 and IL-8. Furthermore, IL-5 and IL-8 induced EO migration, which was also dependent on resident cells and mediated by LTB4. In conclusion, EO migration induced by SAL is dependent on mast cells and MO, whereas that induced by SEP is dependent on mast cells alone. Stimulated mast cells release LTB4, IL-5 and IL-8 while MO release LTB4 and IL-8. The IL-5 and IL-8 release by the SAL or SEP-stimulated resident cells may act in an autocrine fashion, thus potentiating LTB4 release.
有几种实验模型可描述体内嗜酸性粒细胞（EO）的迁移，包括腹腔注射大量生理盐水（SAL）或葡聚糖凝胶珠（SEP）。本研究的目的是探究这两种模型中EO迁移所涉及的机制。每隔48小时连续两次腹腔注射SAL，可诱导EO选择性募集至大鼠腹腔，在最后一次注射后48小时达到峰值。腹腔注射SEP可促进大鼠体内EO聚集。该现象与剂量相关，在注射SEP后48小时达到峰值。为了探究参与此过程的介质，我们发现BW A4C、MK 886和地塞米松（DXA）可抑制SAL和SEP诱导的EO迁移。为了探究EO趋化因子的来源，我们发现，在SAL存在下体外培养的肥大细胞、巨噬细胞（MO）而非淋巴细胞可释放诱导EO迁移的因子。对于SEP，只有肥大细胞释放诱导EO迁移的因子，该因子可被BW A4c、MK 886和DXA抑制。此外，抗白细胞介素-5和白细胞介素-8（IL-5和IL-8）抗血清可抑制SAL刺激的肥大细胞的趋化活性。SAL刺激的MO以及SEP刺激的肥大细胞仅被抗IL-8抗体抑制。这些结果表明，SAL诱导的EO迁移可能依赖于常驻肥大细胞和MO，并由白三烯B4（LTB4）、IL-5和IL-8介导。SEP诱导的EO迁移依赖于肥大细胞，可能由LTB4和IL-8介导。此外，IL-5和IL-8诱导EO迁移，这也依赖于常驻细胞并由LTB4介导。总之，SAL诱导的EO迁移依赖于肥大细胞和MO，而SEP诱导的EO迁移仅依赖于肥大细胞。受刺激的肥大细胞释放LTB4、IL-5和IL-8，而MO释放LTB4和IL-8。SAL或SEP刺激的常驻细胞释放的IL-调节因子5和IL-8可能以自分泌方式起作用，从而增强LTB4的释放。
