Faas M M, Bakker W W, Valkhof N, van der Horst M C, Schuiling G A
Department of Obstetrics and Gynaecology, University of Groningen, The Netherlands.
Biol Reprod. 1997 Jun;56(6):1400-6. doi: 10.1095/biolreprod56.6.1400.
These experiments were designed to study the increased sensitivity of pregnant rats to endotoxin. Pregnant (Pr), cyclic (C), and progesterone (P)-treated pseudopregnant rats with or without a decidualized uterus (PSP and DEC rats, respectively) received infusions of an ultra-low dose of endotoxin (1.0 microg/kg BW) and were killed 3 days later. Pr, PSP, and DEC rats were infused on Day 14, C rats on diestrus. Endotoxin-infused rats were compared with saline-infused rats in the same reproductive conditions. The inflammatory reaction of the glomeruli of the kidneys was studied by immunohistochemical methods using 4-microm cryostat sections stained with specific monoclonal antibodies against neutrophils (polymorphonuclear cells, PMNs) and monocytes (MOs), and against the adhesion molecules ICAM-1 and VCAM-1 on the endothelium, and LFA-1, MAC-1, and VLA-4 on the leukocytes. Endotoxin infusion increased glomerular PMN and MO number in Pr, PSP, and DEC rats, all of which have elevated P levels, but not in C rats, which do not. The endotoxin-induced expression of adhesion molecules, associated with this influx of inflammatory cells, varied with the reproductive condition. In C rats there was no increased adhesion molecule expression after endotoxin treatment, in Pr rats there was increased expression of both the combinations ICAM-1/LFA-1 and VCAM-1/VLA-4. DEC rats did not express either of these combinations (although there was expression of ICAM-1); PSP rats expressed the combination ICAM-1/MAC-1. Adhesion molecule expression thus seems to be regulated by ovarian (e.g., P) and placental factors (e.g., of trophoblastic and decidual origin). Because the different combinations of adhesion molecules in the various reproductive conditions after exposure to endotoxin led to more or less the same leukocyte influx under these conditions, the increased sensitivity to endotoxin of pregnant individuals cannot be reduced to differences in leukocyte influx into the glomeruli.
这些实验旨在研究妊娠大鼠对内毒素敏感性增加的情况。妊娠（Pr）、处于发情周期（C）以及用孕酮（P）处理的假孕大鼠（分别为PSP和DEC大鼠，有无蜕膜化子宫）接受超低剂量内毒素（1.0微克/千克体重）输注，并于3天后处死。Pr、PSP和DEC大鼠在第14天输注，C大鼠在动情后期输注。将输注内毒素的大鼠与处于相同生殖状态下输注生理盐水的大鼠进行比较。使用4微米冰冻切片，通过免疫组织化学方法研究肾脏肾小球的炎症反应，切片用针对中性粒细胞（多形核细胞，PMN）和单核细胞（MO）以及内皮细胞上的黏附分子ICAM-1和VCAM-1、白细胞上的LFA-1、MAC-1和VLA-4的特异性单克隆抗体进行染色。内毒素输注增加了Pr、PSP和DEC大鼠肾小球中的PMN和MO数量，这些大鼠的P水平均升高，但未增加C大鼠（其P水平未升高）的肾小球中的PMN和MO数量。与这种炎症细胞流入相关的内毒素诱导的黏附分子表达随生殖状态而变化。在内毒素处理后，C大鼠的黏附分子表达未增加，Pr大鼠中ICAM-1/LFA-1和VCAM-1/VLA-4这两种组合的表达均增加。DEC大鼠未表达这两种组合中的任何一种（尽管有ICAM-1的表达）；PSP大鼠表达ICAM-1/MAC-1组合。因此，黏附分子的表达似乎受卵巢（如P）和胎盘因子（如滋养层和蜕膜来源的因子）调节。由于在接触内毒素后，不同生殖状态下黏附分子的不同组合在这些条件下导致或多或少相同的白细胞流入，所以妊娠个体对内毒素敏感性增加不能简单归结为白细胞流入肾小球的差异。
