Effect of fibrinogen on leukocyte margination and adhesion in postcapillary venules.

Effect of fibrinogen on leukocyte margination and adhesion in postcapillary venules.
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纤维蛋白原对毛细血管后微静脉白细胞边缘化和粘附的影响。

DOI:
10.1080/10739680490425994
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发表时间:
2004
期刊:
Microcirculation (New York, N.Y. : 1994)
影响因子:
--
通讯作者:
Lipowsky,HerbertH
Lipowsky,HerbertH
中科院分区:
--
文献类型:
--
作者:
Pearson,MarkJ;Lipowsky,HerbertH

文献摘要

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目的定量评价纤维蛋白原(Fb)诱导红细胞(RBC)聚集、降低切变率(γ)和增加WBC与内皮细胞(EC)接触的能力,并探讨Fb作为白细胞(WBC)在毛细血管后微静脉边集决定因子的作用。在全身输注Fb之前和之后,在降低γ后,在大鼠肠系膜毛细血管后微静脉中测量了(EC处的通量)、滚动速度和对EC的粘附。用钝头探针近端闭塞供血微血管有助于γ从600 s-1降低到50 s-1。聚集指数(G)是从RBC的光散射性质导出的,其中G与每个聚集体的RBC数量成比例。白细胞边缘的测定是总管腔WBC流量的百分比,滚动的EC,F*WBC.ResultsFor正常水平的Fb(0.07 g%),γ的减少导致4倍上升inF* WBC和没有变化inGas γ减少到50 s-1。输注Fb使血浆浓度达到0.7 g%,导致G适度增加20%,F *WBCat γ = 50 s−1增加2.5倍。白细胞-内皮细胞粘附出现显着增加,但远远低于与高分子量葡聚糖(Dx)的输液。在低剪切下,Dx使G增加3倍,γ降低,但F * WBC仅增加Fb的一半。在Fb存在下的更大的边集是由促进WBC径向迁移的RBC红细胞叠连引起的。相比之下,从高分子量的Dx夹带白细胞的红细胞团块产生的血浆间隙内沿着血管centerline.ConclusionsIn存在的Fb,白细胞的边缘急剧增加,在低剪切由于红细胞叠连形成,这增强了白细胞的径向迁移。这种效应比Dx大得多,因为Fb诱导的小串的破坏排除了HMICRO的减少,而Dx诱导的聚集体形成等离子体间隙。因此,由增加的Fb引起的适度水平的RCA可极大地增强边缘化,并且随着Fb的增强,在低流动状态下协同地促进稳固的WBC-EC粘附(Microcirculation(2004)11,295 -306)。doi:10.1080/10739680490425994
ObjectiveTo quantitatively evaluate the role of fibrinogen (Fb) as a determinant of leukocyte (WBC) margination in postcapillary venules in light of its ability to induce red blood cell (RBC) aggregation with reductions in shear rate (γ) and increase adhesiveness of WBCs to endothelium (EC).MethodsRed cell aggregation (RCA), WBC margination (flux at the EC), rolling velocity, and adhesion to the EC were measured in rat mesenteric postcapillary venules upon reducing γ, prior to and following systemic infusion of Fb. Proximal occlusion of feeding microvessels with a blunted probe facilitated reductions in γ from 600 to 50 s−1. An index of aggregation (G) was derived from light-scattering properties of RBCs, whereGwas proportional to the number of RBCs per aggregate. WBC margination was measured as the percentage of total luminal WBC flux that rolled on the EC,F*WBC.ResultsFor normal levels of Fb (0.07 g%), reductions in γ resulted in a 4-fold rise inF*WBCand no change inGas γ was reduced to 50 s−1. Infusion of Fb to achieve a plasma concentration to 0.7 g% caused a modest 20% increase inGand a 2.5-fold increase inF*WBCat γ = 50 s−1. WBC-EC adhesion appeared to increase significantly, but much less than with infusion of high molecular weight dextran (Dx). With Dx,Gincreased 3-fold, with reductions in γ, butF*WBCincreased only half the amount incurred with Fb at low shear. The greater margination in the presence of Fb results from RBC rouleaux that promote radial migration of WBCs. In contrast, clumps of RBCs resulting from high molecular weight Dx entrain WBCs within plasma gaps along the vessel centerline.ConclusionsIn the presence of Fb, margination of WBCs increases dramatically at low shear due to rouleaux formation, which enhances radial migration of WBCs. This effect is much greater than with Dx because disruption of the much weaker Fb induced rouleaux precludes reductions inHMICRO, whereas clumping aggregates induced by Dx form plasma gaps. Thus, modest levels of RCA caused by increased Fb may greatly enhance margination and with an enhancement of adhesiveness synergistically promote firm WBC-EC adhesion in the low flow state.Microcirculation(2004)11,295–306. doi:10.1080/10739680490425994