Role of P-selectin in microvascular leukocyte-endothelial interaction in splanchnic ischemia-reperfusion.

Role of P-selectin in microvascular leukocyte-endothelial interaction in splanchnic ischemia-reperfusion.
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P-选择素在内脏缺血再灌注微血管白细胞-内皮相互作用中的作用。

DOI:
10.1152/ajpheart.1994.267.2.h622
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发表时间:
1994
期刊:
The American journal of physiology
影响因子:
--
通讯作者:
Lefer,AM
Lefer,AM
中科院分区:
--
文献类型:
--
作者:
Davenpeck,KL;Gauthier,TW;Albertine,KH;Lefer,AM

文献摘要

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用P-选择素中和单抗(MAb PB1.3)研究了P-选择素在戊巴比妥钠麻醉大鼠内脏动脉阻断再灌注(SAO/R)后白细胞-内皮细胞相互作用中的作用。活体显微镜观察,SAO/R大鼠再灌流前静脉注射MAb PB1.3(1 mg/kg)可显著减少肠系膜毛细血管后小静脉内白细胞的卷曲和黏附。同样,回肠髓过氧化物酶(MPO)活性从未治疗的缺血大鼠的4.6+/-0.6降至2.0+/-0.2U/100 mg(P<0.01),表明中性粒细胞(PMN)聚集程度较轻。经PB1.3单抗处理的大鼠血浆游离氨基氮浓度显著低于未处理的大鼠(P<0.01),表明再灌注后组织损伤减轻。免疫组织化学定位显示,缺血内脏循环再灌流30min后,回肠毛细血管内皮细胞内P-选择素有明显表达。因此,P-选择素在内脏缺血再灌流后白细胞聚集中起重要作用,而单抗PB1.3可减少缺血再灌流小肠中性粒细胞的聚集,从而减轻组织损伤。
The role of P-selectin in leukocyte-endothelial interaction after splanchnic arterial occlusion and reperfusion (SAO/R) in pentobarbital-anesthetized rats was investigated employing a P-selectin-neutralizing monoclonal antibody (i.e., MAb PB1.3). MAb PB1.3 (1 mg/kg) given intravenously to SAO/R rats just before reperfusion significantly attenuated leukocyte rolling and adherence in mesenteric postcapillary venules as observed via intravital microscopy. Likewise, ileal myeloperoxidase (MPO) activity was decreased from 4.6 +/- 0.6 in nontreated ischemic rats to 2.0 +/- 0.2 U/100 mg (P < 0.01), indicating a lesser degree of polymorphonuclear leukocyte (PMN) accumulation. A significantly lower plasma free amino-nitrogen concentration was observed in MAb PB1.3-treated rats vs. untreated (P < 0.01), suggesting decreased tissue injury after reperfusion. Immunohistochemical localization demonstrated significant expression of P-selectin in endothelial cells lining ileal postcapillary venules 30 min after reperfusion of the ischemic splanchnic circulation. Thus P-selectin appears to plays an important role in leukocyte accumulation after splanchnic ischemia-reperfusion, and the MAb PB1.3 attenuates the accumulation of PMNs in the ischemic-reperfused small bowel, resulting in reduced tissue injury.