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2017 ; 8
(32
): 53563-53580
Nephropedia Template TP
gab.com Text
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English Wikipedia
The novel sphingosine-1-phosphate receptors antagonist AD2900 affects lymphocyte
activation and inhibits T-cell entry into the lymph nodes
#MMPMID28881832
Song J
; Dagan A
; Yakhtin Z
; Gatt S
; Riley S
; Rosen H
; Or R
; Almogi-Hazan O
Oncotarget
2017[Aug]; 8
(32
): 53563-53580
PMID28881832
show ga
Sphingolipid derivatives play key roles in immune cell migration and function.
Synthetic sphingolipid analogues are used as therapeutics to intervene various
inflammatory and malignant conditions. We hypothesize that different analogs have
different effects on immune cells and therefore can be used as treatment for
specific diseases. This study examines the properties of the novel synthetic
sphingolipid analog, AD2900, and its effects on immune cell activation and
lymphocyte localization in homeostasis. AD2900 is an antagonist for all
sphingosine-1-phosphate (S1P) receptors. It demonstrates a significant inhibitory
effect on the proliferation of activated human peripheral blood mononuclear
cells, which is dependent on cAMP reduction and calcium signal transduction but
not on phospholipase C activation. AD2900 causes a significant but reversible
downregulation of S1P1 expression on the cell surface. AD2900 administration to
C57BL/6J mice leads to the accumulation of T cells in the blood and spleen and in
turn reduces T-cell number in the lymph nodes. Moreover, AD2900 treatment shows
significant effects on the localization of T-cell subpopulations. These results
demonstrate the key roles of S1P in T-cell trafficking in a steady state and
suggest a potential clinical application for AD2900. Notably, this sphingolipid
analog does not cause a severe lymphopenia. The clinical effect of AD2900 in
hemato-oncologic diseases and immune-related diseases needs further
investigation.