Selective inhibition by rottlerin of macropinocytosis in monocyte-derived dendritic cells

Kakali Sarkar; Michael J. Kruhlak; Stanley L. Erlandsen; Stephen Shaw

doi:10.1111/j.1365-2567.2005.02253.x

Selective inhibition by rottlerin of macropinocytosis in monocyte-derived dendritic cells

Kakali Sarkar, Michael J. Kruhlak, Stanley L. Erlandsen, Stephen Shaw

Research output: Contribution to journal › Article › peer-review

87 Scopus citations

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 (IC₅₀ of 0.4 μM). 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 μM 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.

Original language	English (US)
Pages (from-to)	513-524
Number of pages	12
Journal	Immunology
Volume	116
Issue number	4
DOIs	https://doi.org/10.1111/j.1365-2567.2005.02253.x
State	Published - Dec 2005
Externally published	Yes

Keywords

Antigen presentation
Dendritic cells
Fluid-phase endocytosis
GM-CSF
IL-4
Monocytes
T lymphocytes

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1111/j.1365-2567.2005.02253.x

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title = "Selective inhibition by rottlerin of macropinocytosis in monocyte-derived dendritic cells",

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 (IC50 of 0.4 μM). 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 μM 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 = "Antigen presentation, Dendritic cells, Fluid-phase endocytosis, GM-CSF, IL-4, Monocytes, T lymphocytes",

author = "Kakali Sarkar and Kruhlak, {Michael J.} and Erlandsen, {Stanley L.} and Stephen Shaw",

year = "2005",

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doi = "10.1111/j.1365-2567.2005.02253.x",

language = "English (US)",

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AU - Sarkar, Kakali

AU - Kruhlak, Michael J.

AU - Erlandsen, Stanley L.

AU - Shaw, Stephen

PY - 2005/12

Y1 - 2005/12

N2 - 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 (IC50 of 0.4 μM). 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 μM 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.

AB - 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 (IC50 of 0.4 μM). 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 μM 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.

KW - Antigen presentation

KW - Dendritic cells

KW - Fluid-phase endocytosis

KW - GM-CSF

KW - IL-4

KW - Monocytes

KW - T lymphocytes

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Selective inhibition by rottlerin of macropinocytosis in monocyte-derived dendritic cells

Abstract

Keywords

ASJC Scopus subject areas

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