Abstracts (complete list) - Wissenschaft Online

Andrey Bogdanov, Tatyana Rybakova, Anna Nizkorodova, Nikolay Belyaev
Effect of alpha-fetoprotein-activated hematopoietic stem cells
on monocytes functional activity
I was shown, alpha-fetoprotein (AFP) disturbs certain function of monocytes in vitro and
in vivo models. In our previous work, we discovered AFP as an inductor of mice bone
marrow hematopoietic stem cells (HSCs) suppression activity in vitro. Whether
possibility of AFP-activated HSCs modulates monocytes activity and amplifies direct
effects of AFP is unknown. We investigated effect of AFP-activated mice bone marrow
HSCs on monocytes functions. Our results show that AFP-activated HSCs suppressed
the spontaneous expression as well as inhibited LPS-induced up-regulation of •••I, CR3,
CR4, and especially CD80, CD86, ICAM-1, LFA-1 and •••II. AFP-activated HSCs almost
completely suppressed synthesis of IL-1β, IL-6, IL-12, IL-18 and TNF-α from other site,
they increased IL-10 and TGF-β1 production in monocytes. AFP-activated HSCs
decreased their capacity to secret chemokines as IL-8 and MCP-1 as well as eicosanoids
as leukotriene C4 and prostaglandin D2. However, some HSCs subpopulations increase
prostaglandin E2 production. Analysis of monocytes effector functions presented
number of considerable impairments. The first, HSCs-treated monocytes showed weak
phagocytosis and NO production abilities. The second, both oxygen-dependent and
oxygen-independent potentials of HSCs-treated monocytes were significantly
suppressed. The third, HSCs-treated monocytes inhibited cytotoxic activity of naive NK
cells and CTL, and were not able to stimulate IFN-γ and TNF-α production in them. The
fourth, HSCs-treated monocytes had a weak antigen-presenting capacity for naive CD8
+ T cells. In the end, HSCs-treatment monocytes induced differentiation of naive CD4+
• cells and Th1 cells into Th2 cells. Thus, effect of AFP-activated HSCs on monocytes
contributes to their immunosuppression profile.