|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 95 No. 11 (June 1), 2000:
pp. 3460-3466
Hydroxychloroquine inhibits calcium signals in T cells: a new
mechanism to explain its immunomodulatory properties
Frederick D. Goldman,
Andrew L. Gilman,
Clay Hollenback,
Roberta M. Kato,
Brett A. Premack, and
David J. Rawlings
Department of Pediatrics, University of Iowa, Iowa City; Department
of Pediatrics, Children's Mercy Hospital, University of Missouri-KC,
School of Medicine, Kansas City; Department of Pediatrics, the Jonsson
Comprehensive Cancer Center, and the Molecular Biology Institute and
Department of Physiology, University of California, Los Angeles.
Hydroxychloroquine (HCQ), a lysosomotropic amine, is an
immunosuppressive agent presently being evaluated in bone marrow
transplant patients to treat graft-versus-host disease. While its
immunosuppressive properties have been attributed primarily to its
ability to interfere with antigen processing, recent reports
demonstrate HCQ also blocks T-cell activation in vitro. To more
precisely define the T-cell inhibitory effects of HCQ, the authors
evaluated T-cell antigen receptor (TCR) signaling events in a T-cell
line pretreated with HCQ. In a concentration-dependent manner, HCQ
inhibited anti-TCR-induced up-regulation of CD69 expression, a distal
TCR signaling event. Proximal TCR signals, including inductive protein
tyrosine phosphorylation, tyrosine phosphorylation of phospholipase C
 1, and total inositol phosphate production, were unaffected by HCQ.
Strikingly, anti-TCR-crosslinking-induced calcium mobilization was
significantly inhibited by HCQ, particularly at the highest
concentrations tested (100 µmol/L) in both T-cell lines and primary T cells. HCQ, in a dose-dependent fashion, also reduced a B-cell antigen receptor calcium signal, indicating this effect may be a general property of HCQ. Inhibition of the calcium signal correlated directly with a reduction in the size of
thapsigargin-sensitive intracellular calcium stores in HCQ-treated
cells. Together, these findings suggest that disruption of
TCR-crosslinking-dependent calcium signaling provides an additional
mechanism to explain the immunomodulatory properties of HCQ.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
K. T. Ho, C. W. Ahn, G. S. Alarcon, B. A. Baethge, F. K. Tan, J. Roseman, H. M. Bastian, B. J. Fessler, G. McGwin Jr, L. M. Vila, et al.
Systemic lupus erythematosus in a multiethnic cohort (LUMINA): XXVIII. Factors predictive of thrombotic events
Rheumatology,
October 1, 2005;
44(10):
1303 - 1307.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Knudson, S. Kulkarni, Z. K. Ballas, M. Bessler, and F. Goldman
Association of immune abnormalities with telomere shortening in autosomal-dominant dyskeratosis congenita
Blood,
January 15, 2005;
105(2):
682 - 688.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P-H Huang, T-C Tuan, Y-J Lin, Y-A Ding, and C-W Kong
Letter to the Editor
Lupus,
September 1, 2003;
12(9):
725 - 727.
[PDF]
|
|
|
|
|
|
|
M.-A. Kang, S.-Y. Yun, and J. Won
Rosmarinic acid inhibits Ca2+-dependent pathways of T-cell antigen receptor-mediated signaling by inhibiting the PLC-gamma 1 and Itk activity
Blood,
May 1, 2003;
101(9):
3534 - 3542.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
