Das A M, Flower R J, Perretti M
Department of Biochemical Pharmacology, The William Harvey Research Institute, London, United Kingdom.
J Immunol. 1997 Aug 1;159(3):1466-73.
Cell accumulation in response to i.p. administration of the C-C chemokine, eotaxin, was studied in vivo. OVA-sensitized mice, exhibiting blood eosinophilia, had greater eosinophil (Eø) accumulation in response to 500 ng of eotaxin at 6 h (vehicle-injected, 3.0 +/- 0.5 x 10(5); eotaxin-injected, 8.6 +/- 1.0 x 10(5)) than nonsensitized, eotaxin-injected mice (2.5 +/- 0.4 x 10(5)). A nonspecific neutrophil migration was observed in both vehicle- and eotaxin-injected cavities. The number of intact mast cells in the peritoneal lavages after eotaxin injection was significantly lower than that in vehicle-injected animals (0.8 +/- 0.3 x 10(4) vs 2.8 +/-0.6 x 10(4), respectively). When endogenous peritoneal mast cells were depleted with compound 48/80 before eotaxin administration, there was a 51% reduction in Eø accumulation. This suggests an important role for endogenous mast cells in mediating the actions of eotaxin. The potential role of mast cell mediators in the actions of eotaxin was also investigated. Pretreatment with histamine-H1 or serotonin antagonists reduced Eø migration in response to eotaxin by 50 to 65%. Further, following pretreatment with a specific mAb against TNF-alpha, only nonspecific neutrophil influx was attenuated. Using neutralizing mAbs, Eø migration was found to be dependent on the adhesion molecules P- and E-selectin and CD11b. Eø accumulation was also sensitive to dexamethasone, with doses as low as 0.2 mg/kg inducing 100% inhibition. This study provides useful insight into the mechanisms of action of eotaxin.
在体内研究了腹腔注射C-C趋化因子嗜酸性粒细胞趋化因子后细胞的聚集情况。表现出血液嗜酸性粒细胞增多的卵清蛋白致敏小鼠，在6小时时对500 ng嗜酸性粒细胞趋化因子的反应中，嗜酸性粒细胞（Eø）的聚集量（注射溶媒组为3.0±0.5×10⁵；注射嗜酸性粒细胞趋化因子组为8.6±1.0×10⁵）比未致敏的、注射嗜酸性粒细胞趋化因子的小鼠（2.5±0.4×10⁵）更多。在注射溶媒和嗜酸性粒细胞趋化因子的腔隙中均观察到非特异性中性粒细胞迁移。注射嗜酸性粒细胞趋化因子后腹腔灌洗液中完整肥大细胞的数量显著低于注射溶媒的动物（分别为0.8±0.3×10⁴和2.8±0.6×10⁴）。在给予嗜酸性粒细胞趋化因子之前用化合物48/80清除内源性腹腔肥大细胞后，Eø聚集减少了51%。这表明内源性肥大细胞在介导嗜酸性粒细胞趋化因子的作用中起重要作用。还研究了肥大细胞介质在嗜酸性粒细胞趋化因子作用中的潜在作用。用组胺-H1或5-羟色胺拮抗剂预处理可使对嗜酸性粒细胞趋化因子的Eø迁移减少50%至65%。此外，用抗TNF-α的特异性单克隆抗体预处理后，仅非特异性中性粒细胞流入减弱。使用中和单克隆抗体发现，Eø迁移依赖于黏附分子P-选择素、E-选择素和CD11b。Eø聚集对地塞米松也敏感，低至0.2 mg/kg的剂量即可诱导100%的抑制。本研究为嗜酸性粒细胞趋化因子的作用机制提供了有用的见解。
