TGF-beta 1-stimulated adhesion of human mononuclear phagocytes to fibronectin and laminin is abolished by IFN-gamma: Dependence on alpha 5 beta 1 and beta 2 integrins
TGF-beta 1-stimulated adhesion of human mononuclear phagocytes to fibronectin and laminin is abolished by IFN-gamma: Dependence on alpha 5 beta 1 and beta 2 integrins
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DOI：
10.1006/excr.1996.0026
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发表时间：
1996-01-10
影响因子：
3.7
通讯作者：
Wietzerbin, J
中科院分区：
文献类型：
--
作者：
Bauvois, B;VanWeyenbergh, J;Wietzerbin, J
单核细胞在炎症组织的血管外空间内的迁移受粘附分子和炎症细胞因子的控制。在这项研究中，我们分析了tgf - β 1和ifn - γ调节人活化单核细胞对纤维连接蛋白（FN）和层粘连蛋白（LM）的粘附能力，这是细胞外基质的两种成分。当在没有这两种刺激的情况下培养时，人单核细胞经历了“自发激活”，并粘附在FN和LM上。α 5和β 1整合素阻断抗体抑制了FN的粘附，而β 2阻断抗体阻断了LM的粘附。外源性tgf - β 1分别增加了单核细胞对FN和LM的粘附能力，这与α 5和β 2 mRNA和蛋白质合成水平的增加有关。此外，单核细胞表面α - 5表达增加。相比之下，受外源性ifn - γ刺激的单核细胞失去了与FN结合的能力，这与α 5合成的转录后水平发生的表面α 5表达下调相吻合。虽然ifn - γ处理的单核细胞也显示出粘附LM的能力下降，但β 2 mRNA水平、β 2蛋白合成和β 2细胞表面表达均未发生变化，这表明表面β 2整合素的功能状态发生了改变。此外，当tgf - β 1刺激时，ifn - γ预处理的单核细胞重新获得了与FN和LM结合的能力。相反，ifn - γ降低了最初受tgf - β 1刺激的单核细胞对FN和LM的粘附性。这些体外单核细胞对tgf - β 1和ifn - γ调节的粘附-死亡反应可能反映了炎症部位内单核吞噬细胞的运动性。(C) 1996学术出版社，Inc.
Monocyte migration within the extravascular space of inflamed tissues is controlled by adhesion molecules and inflammatory cytokines. In this study, we analyzed the capacity of TGF-beta 1 and IFN-gamma to regulate adhesion of human activated monocytes to fibronectin (FN) and to laminin (LM), two components of the extracellular matrix. When cultured in the absence of any of these two stimuli, human monocytes underwent ''spontaneous activation'' and adhered to both FN and LM. Adhesion to FN was inhibited in the presence of alpha 5 and beta 1 integrin blocking antibodies, whereas beta 2 blocking antibody blocked attachment to LM. Exogenous TGF-beta 1 increased the adhesive ability of monocytes to FN and to LM, respectively, linked to the increase of alpha 5 and beta 2 mRNA and protein synthesis levels. Moreover, an increase in alpha 5 expression at the monocyte cell surface was observed. In contrast, monocytes stimulated with exogenous IFN-gamma lost their capacity to bind to FN and this coincided with the down-regulation of surface alpha 5 expression which occurred at the posttranscriptional level of alpha 5 synthesis. Although IFN-gamma-treated monocytes also showed a decreased ability to adhere to LM, no alteration of beta 2 mRNA levels, beta 2 protein synthesis, and beta 2 cell surface expression was detectable, thus suggesting a modification of the functional state of surface beta 2 integrins, Furthermore, when stimulated with TGF-beta 1, IFN-gamma-pretreated monocytes reacquired the ability to bind to FN and LM. Conversely, IFN-gamma reduced adhesiveness to FN and LM of monocytes initially stimulated with TGF-beta 1. These in vitro adhesive-deadhesive responses of monocytes to TGF-beta 1 and IFN-gamma modulation may reflect mononuclear phagocyte motility within sites of inflammation. (C) 1996 Academic Press, Inc.