Anti-P-selectin antibody decreases inflammation and thrombus formation in venous thrombosis
Anti-P-selectin antibody decreases inflammation and thrombus formation in venous thrombosis
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DOI：
10.1016/s0741-5214(97)70211-8
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发表时间：
1997-05-01
影响因子：
4.3
通讯作者：
Greenfield, LJ
中科院分区：
文献类型：
--
作者：
Downing, LJ;Wakefield, TW;Greenfield, LJ
目的：静脉血栓与炎症是相互关联的。p -选择素有助于激活白细胞介导的炎症。因此，我们假设p -选择素的中和可以减少静脉壁炎症和血栓形成。方法：12只狒狒采用肾下下腔静脉球囊闭塞术诱导血栓形成。两组4只狒狒在闭塞前和闭塞后第2天和第4天静脉注射抗p选择素抗体（PSab） GA6或CY1748。四只狒狒接受生理盐水控制注射。在第2、6、13天和2个月时，每组一只狒狒被杀死。分析包括静脉造影、超声、钆（Gd）增强磁共振静脉造影（反映静脉壁炎症），以及静脉壁的组织学、形态学和蛋白质评价。评估血栓的存在与否。结果：PSab狒狒第2天时，中下腔静脉和右髂静脉的静脉壁Gd增强减弱（P < 0.05； GA6与对照组相比），2个月后恢复正常。PSab狒狒中下腔静脉中性粒细胞和总白细胞较少；然而，对于右髂静脉的GA6，尽管没有Gd增强，但这些降低并不存在；CY1748使其减少。PSab狒狒的血栓明显少于对照组（p < 0.01， GA6和CY1748与对照组相比）。结论：抗p -选择素抗体可降低静脉壁炎症和血栓形成。抑制p -选择素可能有助于预防静脉血栓形成。
Purpose: Venous thrombosis and inflammation are interrelated. P-selectin contributes to activation of leukocyte-mediated inflammation. Therefore, we hypothesized that the neutralization of P-selectin mould decrease vein wall inflammation and thrombosis.Methods: Twelve baboons underwent infrarenal inferior vena caval balloon occlusion to induce thrombosis. Two groups of four baboons received neutralizing intravenous anti-P-selectin antibody (PSab) GA6 or CY1748 before occlusion and at days 2 and 4. Four baboons received saline control injections. One baboon per group was killed at days 2, 6, and 13, and at 2 months. Analysis included phlebography, ultrasound, gadolinium (Gd)-enhanced magnetic resonance venography (reflecting vein wall inflammation), and histologic, morphometric, and protein evaluation of the vein wall. Thrombus presence or absence was assessed.Results: By day 2 in PSab baboons, vein wall Gd enhancement was decreased in the mid-inferior vena cava and the right iliac vein (P < 0.05; GA6 vs control baboons), normalizing by 2 months. The mid-inferior vena cava revealed fewer neutrophils and total leukocytes in PSab baboons; however, for GA6 in the right iliac vein these decreases were not present despite the absence of Gd enhancement; they were decreased with CY1748. PSab baboons demonstrated significantly less thrombus than control baboons (p < 0.01, GA6 and CY1748 vs control baboons).Conclusions: Anti-P-selectin antibody decreases vein wall inflammation and thrombus formation. Inhibition of P-selectin may be useful in venous thrombosis prophylaxis.