Universidade do Estado do Amazonas, Manaus, Amazonas, Brazil.
PLoS One. 2013 May 28;8(5):e63410. doi: 10.1371/journal.pone.0063410. Print 2013.
Although thrombocytopenia is a hematological disorder commonly reported in malarial patients, its mechanisms are still poorly understood, with only a few studies focusing on the role of platelets phagocytosis.
Thirty-five malaria vivax patients and eight healthy volunteers (HV) were enrolled in the study. Among vivax malaria patients, thrombocytopenia (<150,000 platelets/µL) was found in 62.9% (22/35). Mean platelet volume (MPV) was higher in thrombocytopenic patients as compared to non-thrombocytopenic patients (p = 0.017) and a negative correlation was found between platelet count and MPV (r = -0.483; p = 0.003). Platelets from HV or patients were labeled with 5-chloromethyl fluorescein diacetate (CMFDA), incubated with human monocytic cell line (THP-1) and platelet phagocytosis index was analyzed by flow cytometry. The phagocytosis index was higher in thrombocytopenic patients compared to non-thrombocytopenic patients (p = 0.042) and HV (p = 0.048). A negative correlation was observed between platelet count and phagocytosis index (r = -0.402; p = 0.016). Platelet activation was assessed measuring the expression of P-selectin (CD62-P) in platelets' surface by flow cytometry. No significant difference was found in the expression of P-selectin between thrombocytopenic patients and HV (p = 0.092). After evaluating the cytokine profile (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ and IL-17) in the patients' sera, levels of IL-6, IL-10 and IFN-γ were elevated in malaria patients compared to HV. Moreover, IL-6 and IL-10 values were higher in thrombocytopenic patients than non-thrombocytopenic ones (p = 0.044 and p = 0.017, respectively. In contrast, TNF-α levels were not different between the three groups, but a positive correlation was found between TNF-α and phagocytosis index (r = -0.305; p = 0.037).
CONCLUSION/SIGNIFICANCE: Collectively, our findings indicate that platelet phagocytosis may contribute to thrombocytopenia found in vivax malaria. Finally, we believe that this study opens new avenues to explore the mechanisms involved in platelet dysfunction, commonly found in vivax malaria patients.
虽然血小板减少症是疟疾患者常报告的一种血液学紊乱，但其机制仍知之甚少，只有少数研究关注血小板吞噬作用的作用。
本研究纳入了 35 名间日疟患者和 8 名健康志愿者（HV）。在间日疟患者中，发现 62.9%（22/35）存在血小板减少症（血小板<150,000/μL）。血小板减少症患者的血小板平均体积（MPV）高于非血小板减少症患者（p=0.017），血小板计数与MPV 呈负相关（r=-0.483；p=0.003）。用 5-氯甲基荧光素二乙酸酯（CMFDA）标记 HV 或患者的血小板，将其与人类单核细胞系（THP-1）孵育，并通过流式细胞术分析血小板吞噬指数。与非血小板减少症患者（p=0.042）和 HV（p=0.048）相比，血小板减少症患者的吞噬指数更高。血小板计数与吞噬指数呈负相关（r=-0.402；p=0.016）。通过流式细胞术测量血小板表面 P 选择素（CD62-P）的表达来评估血小板活化。血小板减少症患者与 HV 之间 P 选择素的表达无显著差异（p=0.092）。评估患者血清细胞因子谱（IL-2、IL-4、IL-6、IL-10、TNF-α、IFN-γ 和 IL-17）后，与 HV 相比，疟疾患者的 IL-6、IL-10 和 IFN-γ 水平升高。此外，与非血小板减少症患者相比，血小板减少症患者的 IL-6 和 IL-10 值更高（p=0.044 和 p=0.017）。相反，三组之间 TNF-α 水平无差异，但 TNF-α 与吞噬指数呈正相关（r=0.305；p=0.037）。
结论/意义：总之，我们的研究结果表明，血小板吞噬作用可能导致间日疟中发现的血小板减少症。最后，我们认为这项研究为探索常发生于间日疟患者的血小板功能障碍的机制开辟了新的途径。
