POLYMORPHONUCLEAR LEUKOCYTE BEHAVIOR IN A NONHUMAN PRIMATE FOCAL ISCHEMIA MODEL
POLYMORPHONUCLEAR LEUKOCYTE BEHAVIOR IN A NONHUMAN PRIMATE FOCAL ISCHEMIA MODEL
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DOI：
10.1038/jcbfm.1994.137
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发表时间：
1994-11-01
影响因子：
6.3
通讯作者：
HUGLI, TE
中科院分区：
文献类型：
--
作者：
EMBER, JA;DELZOPPO, GJ;HUGLI, TE
多形核白细胞（PMN）在局灶性脑梗死演变中的作用越来越受到关注。局灶性脑缺血模型的手术制备可能会改变白细胞的反应性，从而使缺血/再灌注后白细胞功能的解释变得困难。已在狒狒模型中前瞻性地检查了手术准备和实验性缺血/再灌注对粒细胞功能的影响。26只青春期雄性狒狒接受了手术准备，其中21只接受了大脑中动脉闭塞/再灌注。另外4只动物作为非手术对照。在手术准备（即，植入大脑中动脉闭塞装置的整个过程）和闭塞/再灌注。应激相关的白细胞总数升高主要归因于循环PMN白细胞数量的增加。价值从13.9 +/- 4.9 × 10（3）/亩上升到27.8 +/- 5.8 × 10（3）/亩，（+/-SD;总白细胞数为4.3 +/- 2.1 × 10（3）至15.9 +/- 4.7 × 10（3）/mu 1（n = 21），p < 0.001，p < 0.001。手术准备对植入手术后24小时分离的PMN白细胞显示极化的能力没有影响（p ≥ 0.4），0（2）（.-）产生，或当用人C5 a刺激时β-葡萄糖醛酸酶释放。对C5 a的趋化反应中度降低在术后7天（闭塞前）内消退。大脑中动脉闭塞3小时和再灌注1小时导致C5 a诱导的极化显著降低。将闭塞前值82 +/-9.7（n = 7）与闭塞/再灌注值58.8 +/-13.7（n = 6; p < 0.05）进行比较。在C5 a诱导的0（2）（.-）和β-葡萄糖醛酸酶释放，以及趋化反应的降低。在非人灵长类动物模型中，可逆的改变（即，趋化性）在7天内消退。相比之下，大脑中动脉闭塞/再灌注与再灌注后1小时观察到的内源性介质C5 a引起的多种粒细胞功能更显着和显着的降低相关。
There is increasing interest in the role of poly morphonuclear (PMN) leukocytes in the evolution of focal cerebral infarction. Surgical preparation of focal cerebral ischemia models may alter leukocyte reactivity and thereby make interpretation of leukocyte function following ischemia/reperfusion difficult. The effects of surgical preparation and of experimental ischemia/reperfusion on granulocyte function have been examined prospectively in a baboon model. Twenty-six adolescent male baboons underwent surgical preparation, of which 21 underwent middle cerebral artery occlusion/reperfusion. Four additional animals served as nonsurgical controls. Peripheral venous blood specimens were taken for performing assays of leukocyte function at defined intervals before and after both the surgical preparation (i.e., the overall procedure for implantation of the middle cerebral artery occlusion device) and occlusion/reperfusion. A stress related elevation in total leukocyte number was attributed mainly to an increase in the number of circulating PMN leukocytes. Values rose from 13.9 +/- 4.9 x 10(3) to 27.8 +/- 5.8 x 10(3)/mu 1, (+/-SD; n = 21) for total leukocyte number, with p < 0.001, and from 4.3 +/- 2.1 x 10(3) to 15.9 +/- 4.7 x 10(3)/mu 1 (n = 21) for PMN leukocytes, with p < 0.001. Surgical preparation had no effect (p greater than or equal to 0.4) on the ability of PMN leukocytes, isolated 24 h after the implantation procedure, to display polarization, 0(2)(.-) production, or p-glucuronidase release when stimulated with human C5a. A moderate decrease in the chemotactic response to C5a resolved within the 7-day postsurgery (preocclusion) period. Three-hour middle cerebral artery occlusion and l-h reperfusion resulted in a significant reduction in C5a-induced polarization. The preocclusion value of 82 +/- 9.7 (n = 7) was compared with the occlusion/reperfusion value at 58.8 +/- 13.7 (n = 6; p < 0.05). A moderate decrease was observed in C5a-induced 0(2)(.-) and P-glucuronidase release, as well as a decrease in the chemotactic response. In the nonhuman primate model, the reversible alterations (i.e., chemotaxis) in granulocyte function that were noted following surgical preparation resolved within 7 days. In contrast, middle cerebral artery occlusion/reperfusion was associated with a more dramatic and significant reduction in multiple granulocyte functions elicited by the endogenous mediator C5a as observed 1 h postreperfusion.