Calmodulin kinase II regulates the maturation and antigen presentation of human dendritic cells

Tara L Herrmann; Craig T Morita; Kelvin Lee; David J Kusner

doi:10.1189/jlb.0205105

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Calmodulin kinase II regulates the maturation and antigen presentation of human dendritic cells

Journal article

Open access

Peer reviewed

Calmodulin kinase II regulates the maturation and antigen presentation of human dendritic cells

Tara L Herrmann, Craig T Morita, Kelvin Lee and David J Kusner

Journal of leukocyte biology, Vol.78(6), pp.1397-1407

12/2005

DOI: 10.1189/jlb.0205105

PMID: 16204647

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Abstract

Dendritic cells (DC) are professional antigen-presenting cells, which activate the adaptive immune system. Upon receiving a danger signal, they undergo a maturation process, which increases their antigen presentation capacity, but the responsible regulatory mechanisms remain incompletely understood. A Ca2+-calmodulin (Cam)-Cam kinase II (CamK II) pathway regulates phagosome maturation in macrophages, and this pathway is inhibited by pathogenic microbes. Our hypothesis is that signal transduction events which control phagosome maturation also regulate antigen presentation. Stimulation of primary human DC or the human DC line KG-1, with particulate antigen, resulted in the activation of CamK II and its localization to the phagosome and plasma membrane. Two mechanistically distinct inhibitors of CamK II significantly reduced DC maturation, as determined by up-regulation of surface costimulatory and major histocompatibility complex (MHC) class II molecules and secretion of cytokines. Confocal microscopy demonstrated that the CamK II inhibitors blocked the antigen-induced increase in total cellular MHC class molecules as well as their trafficking to the plasma membrane. Inhibition of CamK II was associated with decreased presentation of particulate and soluble MHC class II-restricted antigen, with a greater effect on the former. These data support a model in which CamK II regulates critical stages of the maturation and antigen presentation capacity of human DC, particularly in response to stimulation via phagocytosis.

Phagosomes - enzymology

Dendritic Cells - immunology

Humans

Protein Transport - drug effects

Protein Transport - immunology

Signal Transduction - immunology

Dendritic Cells - drug effects

Histocompatibility Antigens Class II - metabolism

Calcium-Calmodulin-Dependent Protein Kinase Type 2

Cell Membrane - drug effects

Phagosomes - drug effects

Cell Line

Phagocytosis - drug effects

Cells, Cultured

Enzyme Inhibitors - pharmacology

Phagocytosis - immunology

Antigen Presentation - immunology

Cell Differentiation - immunology

Cell Membrane - enzymology

Histocompatibility Antigens Class II - immunology

Signal Transduction - drug effects

Cell Differentiation - drug effects

Dendritic Cells - enzymology

Antigens - immunology

Antigen Presentation - drug effects

Antigens - pharmacology

Calcium-Calmodulin-Dependent Protein Kinases - metabolism

Details

Title: Subtitle: Calmodulin kinase II regulates the maturation and antigen presentation of human dendritic cells
Creators: Tara L Herrmann - Department of Internal Medicine, University of Iowa Carver College of Medicine, Coralville, IA 52241, and Iowa City Veterans Affairs Medical Center, Iowa City, IA, USA
Craig T Morita
Kelvin Lee
David J Kusner
Resource Type: Journal article
Publication Details: Journal of leukocyte biology, Vol.78(6), pp.1397-1407
DOI: 10.1189/jlb.0205105
PMID: 16204647
NLM abbreviation: J Leukoc Biol
ISSN: 0741-5400
eISSN: 1938-3673
Grant note: R01 AR45504 / NIAMS NIH HHS R01 AI055916 / NIAID NIH HHS R01 GM62302 / NIGMS NIH HHS
Language: English
Date published: 12/2005
Academic Unit: Immunology; Internal Medicine
Record Identifier: 9984094501602771

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