Murine stress-triggered abortion is mediated by increase of CD8+ TNF-α+ decidual cells via substance P

被引:60
作者
Joachim, RA [1 ]
Hildebrandt, M [1 ]
Oder, J [1 ]
Klapp, BF [1 ]
Arck, PC [1 ]
机构
[1] Humboldt Univ, Dept Internal Med, Berlin, Germany
关键词
CBA x DBA murine abortion model; flow cytometry; sonic stress; substance PNK1 receptor antagonist;
D O I
10.1111/j.8755-8920.2001.450506.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
PROBLEM: Stress is known to induce abortions in mice and humans. Increased levels of abortogenic type I helper T-cell cytokines and decreased levels of pregnancy protective cytokines could be linked to stress-triggered embryonic loss. Stress promotes neurotransmitter substance P (SP) release in tissues. SP increases the production of decidual tumor necrosis factor (TNF)-alpha whereby the phenotype of these TNF-alpha -producing cells is hypothetical. The objective of the present study was to identify decidual TNF-alpha -producing cell populations that are involved in stress-induced murine abortion. METHOD: DBA/2J-mated CBA/J female mice were exposed to ultrasonic sound stress on day 5.5 of pregnancy. The mice were randomized and half were treated with the SP NK1-receptor antagonist (SP-RA) RP 67580 (200 mug/mouse). Frequency and cytokine profile of CD8(+) cells were evaluated by immunohistochemistry and flow cytometry. Degranulation of uterine mast cells was examined histologically. RESULTS: On day 13.5 of pregnancy, the uteri were removed and the resorption rate was calculated. A mean resorption rate of 38.4% was detected in stressed mice (n = 10) compared to 13.1% in non-stressed control mice (n = 11, P < 0.01). Injection of SP-RA decreased the abortion rate to 18.4% in stressed mice (n = 19, P < 0.01). Flow cytometry revealed a stress-related increase of TNF-alpha (+)/CD8(+) decidual T cells, which could be abrogated by SP-RA (P < 0.05). No significant differences could be observed in numbers of mast cells and total CD8(+) cells in situ. CONCLUSION: Our data suggest that stress-triggered abortion is mediated by SP, and SP receptor blockade abrogates stress-triggered abortion via reduced production of TNF-<alpha> by CD8(+) T cells.
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收藏
页码:303 / 309
页数:7
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