Ramos C D L, Heluy-Neto N E, Ribeiro R A, Ferreira S H, Cunha F Q
Department of Pharmacology, Faculty of Medicine of Ribeirão Preto, University of São Paulo-USP, Avenida Bandeirantes 3900, Ribeirão Preto, Sao Paulo 14049-900, Brazil.
Cytokine. 2003 Mar 7;21(5):214-23. doi: 10.1016/s1043-4666(03)00050-4.
The aim of this study was to characterize the mediators released by mast cells responsible for IL-8-induced neutrophil migration. It was observed that IL-8 induces a dose-dependent neutrophil migration into peritoneal cavity of rats, but not into air-pouch cavity in which resident mast cells are not present. The transference of peritoneal mast cells to the air-pouch renders this cavity responsive to IL-8. The neutrophil migration induced by IL-8 into the peritoneal cavity was not observed when the peritoneal-resident mast cells were depleted by compound 48/80 or distilled water treatment. Confirming the importance of mast cells, IL-8-stimulated mast cells supernatant induced significant neutrophil migration when injected into peritoneal and air-pouch cavities. The IL-8-induced neutrophil migration was observed not to be dependent on LTB(4), prostaglandins or TNF-alpha, since MK886, indomethacin or thalidomide were unable to block the IL-8-induced neutrophil accumulation 'in vivo' or the release of neutrophil chemotactic factor "in vitro" by IL-8-stimulated mast cells. However, dexamethasone, an inhibitor of the synthesis of pro-inflammatory cytokines, blocked the neutrophil migration induced by IL-8 "in vivo" and also inhibited the release of the neutrophil chemotactic factor by IL-8-stimulated mast cells. Moreover, the incubation of IL-8-stimulated mast cells supernatant with antibody against cytokine-induced neutrophil chemoattractant 1 (CINC-1), but not against TNF-alpha or IL-1beta, inhibited its neutrophil chemotactic activity. Furthermore, we found a significant amount of CINC-1 in this supernatant. In conclusion, we demonstrated that the neutrophil migration induced by IL-8 is dependent on CINC-1 release from mast cells.
本研究的目的是鉴定负责白细胞介素-8（IL-8）诱导的中性粒细胞迁移的肥大细胞释放的介质。据观察，IL-8可诱导大鼠腹腔内中性粒细胞呈剂量依赖性迁移，但不会诱导迁移至不存在驻留肥大细胞的气囊肿腔内。将腹腔肥大细胞转移至气囊肿可使该腔对IL-8产生反应。当用化合物48/80或蒸馏水处理使腹腔驻留肥大细胞耗竭时，未观察到IL-8诱导的中性粒细胞向腹腔内迁移。证实了肥大细胞的重要性，当将IL-8刺激的肥大细胞上清液注射到腹腔和气囊肿腔内时，可诱导显著的中性粒细胞迁移。观察到IL-8诱导的中性粒细胞迁移不依赖于白三烯B4（LTB4）、前列腺素或肿瘤坏死因子-α（TNF-α），因为MK886、吲哚美辛或沙利度胺无法在“体内”阻断IL-8诱导的中性粒细胞聚集或在“体外”阻断IL-8刺激的肥大细胞释放中性粒细胞趋化因子。然而，作为促炎细胞因子合成抑制剂的地塞米松在“体内”阻断了IL-8诱导的中性粒细胞迁移，并且还抑制了IL-8刺激的肥大细胞释放中性粒细胞趋化因子。此外，用抗细胞因子诱导的中性粒细胞趋化因子1（CINC-1）抗体而非抗TNF-α或IL-1β抗体孵育IL-8刺激的肥大细胞上清液，可抑制其对中性粒细胞的趋化活性。此外，我们在该上清液中发现了大量的CINC-1。总之，我们证明了IL-8诱导的中性粒细胞迁移依赖于肥大细胞释放CINC-1。
