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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Immunotoxicol
2015 ; 12
(2
): 181-7
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Accelerator mass spectrometry detection of beryllium ions in the antigen
processing and presentation pathway
#MMPMID24932923
Tooker BC
; Brindley SM
; Chiarappa-Zucca ML
; Turteltaub KW
; Newman LS
J Immunotoxicol
2015[Apr]; 12
(2
): 181-7
PMID24932923
show ga
Exposure to small amounts of beryllium (Be) can result in beryllium sensitization
and progression to Chronic Beryllium Disease (CBD). In CBD, beryllium is
presented to Be-responsive T-cells by professional antigen-presenting cells
(APC). This presentation drives T-cell proliferation and pro-inflammatory
cytokine (IL-2, TNF?, and IFN?) production and leads to granuloma formation. The
mechanism by which beryllium enters an APC and is processed to become part of the
beryllium antigen complex has not yet been elucidated. Developing techniques for
beryllium detection with enough sensitivity has presented a barrier to further
investigation. The objective of this study was to demonstrate that Accelerator
Mass Spectrometry (AMS) is sensitive enough to quantify the amount of beryllium
presented by APC to stimulate Be-responsive T-cells. To achieve this goal, APC -
which may or may not stimulate Be-responsive T-cells - were cultured with
Be-ferritin. Then, by utilizing AMS, the amount of beryllium processed for
presentation was determined. Further, IFN? intracellular cytokine assays were
performed to demonstrate that Be-ferritin (at levels used in the experiments)
could stimulate Be-responsive T-cells when presented by an APC of the correct HLA
type (HLA-DP0201). The results indicated that Be-responsive T-cells expressed
IFN? only when APC with the correct HLA type were able to process Be for
presentation. Utilizing AMS, it was determined that APC with HLA-DP0201 had
membrane fractions containing 0.17-0.59?ng Be and APC with HLA-DP0401 had
membrane fractions bearing 0.40-0.45?ng Be. However, HLA-DP0401 APC had 20-times
more Be associated with the whole cells (57.68-61.12?ng) than HLA-DP0201 APC
(0.90-3.49?ng). As these findings demonstrate, AMS detection of picogram levels
of Be processed by APC is possible. Further, regardless of form, Be requires
processing by APC to successfully stimulate Be-responsive T-cells to generate
IFN?.