Brandes M E, Mai U E, Ohura K, Wahl S M
Cellular Immunology Section, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892.
J Immunol. 1991 Sep 1;147(5):1600-6.
Participation of human polymorphonuclear neutrophils in the inflammatory response is mediated, in part, by soluble factors such as chemotactic peptides and cytokines. Although the cytokine, transforming growth factor beta (TGF-beta), has been shown to recruit monocytes and promote the inflammatory process, its effects on neutrophils are unknown. In this investigation, [125I]TGF-beta 1 affinity binding studies were employed to show that neutrophils express TGF-beta receptors (350 +/- 20 receptors/cell), which exhibit high affinity for the ligand (dissociation constant, 50 pM). Affinity cross-linking studies identified the receptors to be primarily of the type I class. In contrast to the receptors on monocytes, neutrophil TGF-beta receptors were not down-regulated by exposure to specific inflammatory mediators. Additional studies examined whether exposure of neutrophils to TGF-beta could enhance specific functions, as occurs with monocytes. TGF-beta was shown to cause directed migration of neutrophils at femtomolar concentrations, thus it is the most potent neutrophil chemotactic factor yet identified. Neutrophil production of reactive oxygen intermediates was not stimulated by TGF-beta, nor did TGF-beta enhance or depress subsequent PMA- or FMLP-stimulated superoxide production. However, the stable expression of neutrophil TGF-beta receptors, and the capacity of this cytokine to stimulate neutrophil chemotaxis, suggest that the pro-inflammatory effects of TGF-beta are mediated by neutrophils in addition to monocytes.
人类多形核中性粒细胞参与炎症反应部分是由趋化肽和细胞因子等可溶性因子介导的。尽管细胞因子转化生长因子β（TGF-β）已被证明可募集单核细胞并促进炎症过程，但其对中性粒细胞的影响尚不清楚。在本研究中，采用[125I]TGF-β1亲和结合研究表明中性粒细胞表达TGF-β受体（350±20个受体/细胞），该受体对配体具有高亲和力（解离常数为50 pM）。亲和交联研究确定这些受体主要为I型。与单核细胞上的受体不同，中性粒细胞TGF-β受体不会因暴露于特定炎症介质而下调。其他研究检查了中性粒细胞暴露于TGF-β是否能像单核细胞那样增强特定功能。结果表明，TGF-β在飞摩尔浓度下可引起中性粒细胞定向迁移，因此它是迄今发现的最有效的中性粒细胞趋化因子。TGF-β不会刺激中性粒细胞产生活性氧中间体，也不会增强或抑制随后佛波酯或N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸刺激的超氧化物生成。然而，中性粒细胞TGF-β受体的稳定表达以及该细胞因子刺激中性粒细胞趋化的能力表明，TGF-β除了通过单核细胞介导炎症作用外，还可通过中性粒细胞介导。
