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白细胞介素-8(IL-8)对T淋巴细胞的募集作用。IL-8诱导的中性粒细胞脱颗粒在体外和体内均能释放对人T淋巴细胞有强大作用的趋化因子。

T lymphocyte recruitment by interleukin-8 (IL-8). IL-8-induced degranulation of neutrophils releases potent chemoattractants for human T lymphocytes both in vitro and in vivo.

作者信息

Taub D D, Anver M, Oppenheim J J, Longo D L, Murphy W J

机构信息

Clinical Services Program, SAIC-Frederick, Fredrick Cancer Research And Development Center-National Cancer Institute, MD 21702-1201.

出版信息

J Clin Invest. 1996 Apr 15;97(8):1931-41. doi: 10.1172/JCI118625.

Abstract

IL-8 has been shown to be a human neutrophil and T cell chemoattractant in vitro. In an effort to assess the in vivo effects of IL-8 on human leukocyte migration, we examined the ability of rhIL-8 to induce human T cell infiltration using a human/mouse model in which SCID mice were administered human peripheral blood lymphocytes intraperitoneally, followed by subcutaneous injections of rhIL-8. rhIL-8 induced predominantly murine neutrophil accumulation by 4 h after administration while recombinant human macrophage inflammatory protein-1beta (rhMIP-1beta) induced both murine monocytes and human T cell infiltration during the same time period as determined by immunohistology. Interestingly, 72 h after chemokine administration, a marked human T cell infiltrate was observed in the IL-8 injection site suggesting that rhIL-8 may be acting indirectly possibly through a murine neutrophil-derived T cell chemoattractant. This hypothesis was confirmed using granulocyte-depleted SCID mice. Moreover, human neutrophils stimulated in vitro with IL-8 were found to release granule-derived factor(s) that induce in vitro T cell and monocyte chemotaxis and chemokinesis. This T cell and monocyte chemotactic activity was detected in extracts of both azurophilic and specific granules. Together, these results demonstrate that neutrophils store and release, upon stimulation with IL-8 or other neutrophil activators, chemoattractants that mediate T cell and monocyte accumulation at sites of inflammation.

摘要

白细胞介素-8(IL-8)在体外已被证明是一种人类中性粒细胞和T细胞趋化因子。为了评估IL-8对人类白细胞迁移的体内作用,我们使用人/小鼠模型研究了重组人IL-8(rhIL-8)诱导人类T细胞浸润的能力,该模型中给SCID小鼠腹腔注射人类外周血淋巴细胞,随后皮下注射rhIL-8。给药后4小时,rhIL-8主要诱导鼠中性粒细胞聚集,而重组人巨噬细胞炎性蛋白-1β(rhMIP-1β)在同一时间段内诱导鼠单核细胞和人类T细胞浸润,这是通过免疫组织学确定的。有趣的是,趋化因子给药72小时后,在IL-8注射部位观察到明显的人类T细胞浸润,表明rhIL-8可能通过鼠中性粒细胞衍生的T细胞趋化因子间接起作用。使用粒细胞耗竭的SCID小鼠证实了这一假设。此外,发现体外经IL-8刺激的人类中性粒细胞释放颗粒衍生因子,这些因子可诱导体外T细胞和单核细胞趋化和趋动。在嗜天青颗粒和特异性颗粒的提取物中均检测到这种T细胞和单核细胞趋化活性。总之,这些结果表明,中性粒细胞在受到IL-8或其他中性粒细胞激活剂刺激后储存并释放趋化因子,这些趋化因子介导T细胞和单核细胞在炎症部位的聚集。

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