Platelet Activating Factor Contributes to Vascular Leak in Acute Dengue Infection
Platelet Activating Factor Contributes to Vascular Leak in Acute Dengue Infection
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DOI：
10.1371/journal.pntd.0003459
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发表时间：
2015-02-01
影响因子：
3.8
通讯作者：
Malavige, Gathsaurie Neelika
中科院分区：
文献类型：
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作者：
Jeewandara, Chandima;Gomes, Laksiri;Malavige, Gathsaurie Neelika
尽管血浆渗漏是严重登革热感染的标志，但引起血管通透性增加的因素尚未确定。由于血小板活化因子（PAF）与血管通透性增加，在其他疾病中，我们着手调查其在急性登革热infection.Materials和MethodsPAF水平的作用，初步评估25例急性登革热感染，以确定他们是否在急性登革热增加。为了研究PAF的动力学，在36例患者中评估了系列PAF值。利用人内皮细胞系（HUVECs）检测登革热血清对紧密连接蛋白ZO-1的影响。登革血清和跨内皮电阻（TEER）的影响也测定HUVECs.ResultsPAF水平显着高于急性登革患者（n = 25; p = 0.001）相比，健康人（n = 12）。在对患者（n = 36）系列血液样本中PAF动力学的进一步研究中，PAF水平在临界期开始前升高。与病情较轻的患者相比，在整个疾病过程中有血管渗漏证据的患者的PAF水平显著较高。登革热患者血清显著下调紧密连接蛋白ZO-1（p = 0.004）、HUVEC的表达。使用PAF受体（PAFR）阻滞剂可显著抑制（p = 0.004）。从登革热患者的血清也显着降低TEER，这种减少也显着（p = 0.02）抑制由先前的孵育与PAFR blocker.ConclusionOur结果表明PAF可能是起着重要作用，诱导血管渗漏在急性登革热感染，这提供了一个潜在的治疗干预的目标。
BackgroundAlthough plasma leakage is the hallmark of severe dengue infections, the factors that cause increased vascular permeability have not been identified. As platelet activating factor (PAF) is associated with an increase in vascular permeability in other diseases, we set out to investigate its role in acute dengue infection.Materials and MethodsPAF levels were initially assessed in 25 patients with acute dengue infection to determine if they were increased in acute dengue. For investigation of the kinetics of PAF, serial PAF values were assessed in 36 patients. The effect of dengue serum on tight junction protein ZO-1 was determined by using human endothelial cell lines (HUVECs). The effect of dengue serum on and trans-endothelial resistance (TEER) was also measured on HUVECs.ResultsPAF levels were significantly higher in patients with acute dengue (n = 25; p = 0.001) when compared to healthy individuals (n = 12). In further investigation of the kinetics of PAF in serial blood samples of patients (n = 36), PAF levels rose just before the onset of the critical phase. PAF levels were significantly higher in patients with evidence of vascular leak throughout the course of the illness when compared to those with milder disease. Serum from patients with dengue significantly down-regulated expression of tight junction protein, ZO-1 (p = 0.004), HUVECs. This was significantly inhibited (p = 0.004) by use of a PAF receptor (PAFR) blocker. Serum from dengue patients also significantly reduced TEER and this reduction was also significantly (p = 0.02) inhibited by prior incubation with the PAFR blocker.ConclusionOur results suggest the PAF is likely to be playing a significant role in inducing vascular leak in acute dengue infection which offers a potential target for therapeutic intervention.