Selective inhibition by rottlerin of macropinocytosis in monocyte‐derived dendritic cells
- 7 October 2005
- journal article
- Published by Wiley in Immunology
- Vol. 116 (4) , 513-524
- https://doi.org/10.1111/j.1365-2567.2005.02253.x
Abstract
We present here the analysis of fluid-phase endocytosis (FPE) in human blood monocytes and monocyte-derived dendritic cells (MDDC) facilitated by our serendipitous identification of rottlerin as an efficient inhibitor of dendritic cell FPE (IC(50) of 0.4 microM). Rottlerin was found to be an excellent tool for FPE analysis: rapid-acting, irreversible and selective for FPE (as opposed to receptor-mediated endocytosis) at concentrations of 3 microM and below. The inhibitory effect was not due to toxicity or visible change in membrane ruffles, but affects on cytoskeletal reorganization were evident in MDDC treated with relevant rottlerin concentrations during adhesion. A marked increase in FPE was observed in 1 hr interleukin (IL)-4 and granulocyte macrophage-colony stimulating factor (GM-CSF)-stimulated monocytes. Moreover, rottlerin inhibited the augmented FPE of 1-day cytokine treated monocytes and their augmented ability to induce T cell proliferative responses to tetanus toxoid. We conclude that rottlerin is a useful tool for investigating FPE and its functional importance.Keywords
This publication has 52 references indexed in Scilit:
- Sorting of tropomyosin isoforms in synchronised NIH 3T3 fibroblasts: Evidence for distinct microfilament populationsCell Motility, 2000
- Specificity and mechanism of action of some commonly used protein kinase inhibitorsBiochemical Journal, 2000
- Localization of p21-Activated Kinase 1 (PAK1) to Pinocytic Vesicles and Cortical Actin Structures in Stimulated CellsThe Journal of cell biology, 1997
- Class I MHC presentation of exogenous soluble antigen via macropinocytosis in bone marrow macrophagesImmunity, 1995
- Dendritic cells use macropinocytosis and the mannose receptor to concentrate macromolecules in the major histocompatibility complex class II compartment: downregulation by cytokines and bacterial products.The Journal of Experimental Medicine, 1995
- Membrane ruffling and signal transductionBioEssays, 1994
- Rottlerin, a Novel Protein Kinase InhibitorBiochemical and Biophysical Research Communications, 1994
- Elongation factor‐2 kinase: effective inhibition by the novel protein kinase inhibitor rottlerin and relative insensitivity towards staurosporineFEBS Letters, 1994
- The PKC-Inhibitor RO 31-8220 Selectively Suppresses PMA- and Diacylglycerol-Induced Fluid Pinocytosis and Actin Polymerization in PMNSBiochemical and Biophysical Research Communications, 1993
- The small GTP-binding protein rac regulates growth factor-induced membrane rufflingCell, 1992