| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Published online before print October 4, 2005
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
,
,¶,||,**,1
* The Inflammation Program, Divisions of
¶ Infectious Diseases and
Rheumatology,
|| Departments of Internal Medicine, Physiology and Biophysics, and the Graduate Programs in
Immunology and
** Molecular Biology, University of Iowa Carver College of Medicine and Iowa City Veterans Affairs Medical Center, Iowa City, Iowa; and
Department of Microbiology and Immunology, University of Miami, Florida
1 Correspondence: Inflammation Program, University of Iowa Carver College of Medicine, 2501 Crosspark Rd., D-156, MTF, Coralville, IA 52241. E-mail: david-kusner{at}uiowa.edu
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.
Key Words: signal transduction • cell differentiation • antigen presentation/processing • cytokines • MHC
This article has been cited by other articles:
|
|
 |
|
  M. Illario, M. L. Giardino-Torchia, U. Sankar, T. J. Ribar, M. Galgani, L. Vitiello, A. M. Masci, F. R. Bertani, E. Ciaglia, D. Astone, et al. Calmodulin-dependent kinase IV links Toll-like receptor 4 signaling with survival pathway of activated dendritic cells Blood, January 15, 2008; 111(2): 723 - 731. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. L. Herrmann, R. S. Agrawal, S. F. Connolly, R. L. McCaffrey, J. Schlomann, and D. J. Kusner MHC Class II levels and intracellular localization in human dendritic cells are regulated by calmodulin kinase II J. Leukoc. Biol., September 1, 2007; 82(3): 686 - 699. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Schultz, J. Hume, D. S. Zhang, T. L. Gioannini, and J. P. Weiss A Novel Role for the Bactericidal/Permeability Increasing Protein in Interactions of Gram-Negative Bacterial Outer Membrane Blebs with Dendritic Cells J. Immunol., August 15, 2007; 179(4): 2477 - 2484. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Roychowdhury, P. M. Vyas, and C. K. Svensson Formation and Uptake of Arylhydroxylamine-Haptenated Proteins in Human Dendritic Cells Drug Metab. Dispos., April 1, 2007; 35(4): 676 - 681. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
