Luttmann W, Franz P, Matthys H, Virchow J C
Department of Pneumology, Medical University Clinics, Freiburg, Germany.
Scand J Immunol. 1998 Feb;47(2):127-30. doi: 10.1046/j.1365-3083.1998.00298.x.
Transforming growth factor-beta (TGF-beta), which can decrease the effects of interleukin (IL)-3, IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) on eosinophil viability, has been shown to be chemotactic for neutrophils. However, there is little information on its effects on eosinophil chemotaxis. Because TGF-beta has recently been found in increased concentrations in asthmatic sputum, we investigated whether TGF-beta could influence eosinophil migration and eosinophil viability. Purified eosinophils from normal donors were incubated with increasing concentrations of TGF-beta. Chemotaxis was measured with a modified Boyden chamber technique. In addition, eosinophils were incubated for 96 h with either IL-3, IL-5 or GM-CSF (1 ng/ml) together with increasing concentrations of TGF-beta. Eosinophil viability was then determined with propidium jodide and flow cytometry. Eosinophil chemotaxis was significantly increased in the presence of TGF-beta in concentrations between 10(-9) and 10(-4) microg/ml. The optimal concentration of TGF-beta in this assay was between 10(-9) and 10(-8) microg/ml. The chemotactic effect of TGF-beta diminished when higher as well as lower concentrations (between 10[-12] and 10[-3] microg/ml) were employed. In contrast, inhibition of eosinophil survival induced by IL-3, IL-5 and GM-CSF reached its maximum at concentrations of TGF-beta between 10(-4) and 10(-3) microg/ml. From these data we conclude that TGF-beta in low concentrations can induce eosinophil chemotaxis whereas higher concentrations reduce eosinophil survival mediated by IL-3, IL-5 and GM-CSF.
转化生长因子-β(TGF-β)能够降低白细胞介素(IL)-3、IL-5和粒细胞-巨噬细胞集落刺激因子(GM-CSF)对嗜酸性粒细胞活力的影响,已被证明对中性粒细胞具有趋化作用。然而,关于其对嗜酸性粒细胞趋化性的影响却知之甚少。由于最近发现哮喘患者痰液中TGF-β的浓度升高,我们研究了TGF-β是否会影响嗜酸性粒细胞的迁移和活力。将来自正常供体的纯化嗜酸性粒细胞与浓度不断增加的TGF-β一起孵育。采用改良的Boyden小室技术测量趋化性。此外,将嗜酸性粒细胞与IL-3、IL-5或GM-CSF(1 ng/ml)以及浓度不断增加的TGF-β一起孵育96小时。然后用碘化丙啶和流式细胞术测定嗜酸性粒细胞的活力。在浓度为10^(-9)至10^(-4)微克/毫升的TGF-β存在下,嗜酸性粒细胞趋化性显著增加。该试验中TGF-β的最佳浓度在10^(-9)至10^(-8)微克/毫升之间。当使用更高和更低浓度(10^[-12]至10^[-3]微克/毫升之间)的TGF-β时,其趋化作用减弱。相反,TGF-β对IL-3、IL-5和GM-CSF诱导的嗜酸性粒细胞存活的抑制作用在浓度为10^(-4)至10^(-3)微克/毫升时达到最大。从这些数据我们得出结论,低浓度的TGF-β可诱导嗜酸性粒细胞趋化,而高浓度则降低由IL-3、IL-5和GM-CSF介导的嗜酸性粒细胞存活。