State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China
*: zhouwx@bmi.ac.cn (WX Zhou),
zhangyx@bmi.ac.cn (YX Zhang).
纸质出版:2014-09
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The injury progression of T lymphocytes in a mouse model with subcutaneous injection of a high dose of sulfur mustard[J]. MMR, 2014,1(3):162-172.
Mei et al.: The injury progression of T lymphocytes in a mouse model with subcutaneous injection of a high dose of sulfur mustard. Mil Med Res 2014, 1: 28
The injury progression of T lymphocytes in a mouse model with subcutaneous injection of a high dose of sulfur mustard[J]. MMR, 2014,1(3):162-172. DOI: 10.1186/s40779-014-0028-8.
Mei et al.: The injury progression of T lymphocytes in a mouse model with subcutaneous injection of a high dose of sulfur mustard. Mil Med Res 2014, 1: 28 DOI: 10.1186/s40779-014-0028-8.
Background:
2
In clinical studies
the findings on sulfur mustard (SM) toxicity for CD3
+
CD4
+
and CD3
+
CD8
+
T lymphocyte subsets are contradictory. In animal experiments
the effect of SM on the T cell number and proliferation is incompatible and is even the opposite of the results in human studies. In this study
we observed the dynamic changes of T lymphocytes in the first week in a high-dose SM-induced model.
Methods:
2
Mice were exposed to SM by subcutaneous injection (20 mg/kg) and were sacrificed 4 h
24 h
72 h and 168 h later. Spleen T lymphocyte proliferation was evaluated by
3
H-TdR. Flow cytometric analysis was used to observe the percentage of CD3
+
CD4
+
and CD3
+
CD8
+
T lymphocyte subsets. The IL-1β
IL-6
IL-10 and TNF-α levels in plasma were assayed using the Luminex method. DNA damage in bone marrow cells was observed with the single cell gel electrophoresis technique (SCGE).
Results:
2
SM continuously inhibited the proliferation of lymphocytes for 7 days
and there was a significant rebound of Con A-induced T lymphocyte proliferation only at 24 h. The percentage of CD3
+
CD4
+
and CD3
+
CD8
+
lymphocytes was upregulated
which was accompanied by increased IL-1β and TNF-α and decreased IL-10. The IL-6 level was gradually decreased in the PG group at 4 h. The peak of lymphocytic apoptosis and DNA damage occurred at 24 h and 72 h
respectively.
Conclusion:
2
Our results show that SM significantly inhibited T lymphocyte proliferation as well as induced CD3
+
CD4
+
and CD3
+
CD8
+
upregulation. SM intoxication also significantly increased the levels of pro-inflammatory cytokines (IL-1β
IL-6 and TNF-α) and inhibited the level of anti-inflammatory cytokine IL-10. Our results may partly be due to the significant SM induced significant apoptosis and necrosis of lymphocytes as well as DNA damage of bone marrow cells. The results provided a favorable evaluation of SM immune toxicity in an animal model.
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