Porta J, Carota A, Pizzolato G P, Wildi E, Widmer M C, Margairaz C, Grau G E
Department of Pathology, CMU, University of Geneva, Switzerland.
Clin Neuropathol. 1993 May-Jun;12(3):142-6.
Pathogenic mechanisms in human cerebral malaria remain unclear. We reevaluate the role of cell-mediated immune mechanisms in the pathogenesis of this disease based on autopsy findings in a 34-year-old Caucasian male. Histologic examination of brain tissue showed typical features of severe malaria infection (sequestration of Plasmodium falciparum-infected erythrocytes in vessels, cerebral oedema, petechial lesions and Dürck granulomas). In addition to these classical changes, we found that leukocytes that stained positively in immunohistochemistry for CD68 and tumor necrosis factor-alpha (TNF) coexisted with infected erythrocytes in capillaries, whereas in venules the monocyte population outnumbered the erythrocytes. Notable expression of ICAM-1 on endothelial cell surface was detected by immunohistochemistry in vessels with sequestered cells but not in unaffected vessels. These changes are identical to those of the murine model of the disease, in which cell-mediated immune mechanisms and TNF have been implicated. In vitro, ICAM-1 has been shown to be a potential ligand for P. falciparum-infected erythrocytes. In malaria patients, high serum TNF levels, which have been detected in close correlation with disease severity, may thus favor adhesion to endothelial cells of either red or white blood cells via enhanced ICAM-1 expression. The present observations are further evidence for a role of cell-mediated immunity in the pathogenesis of human cerebral malaria.
人类脑型疟疾的发病机制仍不清楚。我们根据一名34岁白种男性的尸检结果，重新评估细胞介导的免疫机制在该疾病发病过程中的作用。脑组织的组织学检查显示出严重疟疾感染的典型特征（恶性疟原虫感染的红细胞在血管中滞留、脑水肿、瘀点病变和杜尔克肉芽肿）。除了这些经典变化外，我们发现免疫组化中CD68和肿瘤坏死因子-α（TNF）染色呈阳性的白细胞与毛细血管中的感染红细胞共存，而在小静脉中单核细胞数量超过红细胞。免疫组化检测发现，在有滞留细胞的血管内皮细胞表面有明显的细胞间黏附分子-1（ICAM-1）表达，而在未受影响的血管中则没有。这些变化与该疾病的小鼠模型相同，在小鼠模型中细胞介导的免疫机制和TNF已被牵连其中。在体外，ICAM-1已被证明是恶性疟原虫感染红细胞的潜在配体。在疟疾患者中，已检测到高血清TNF水平与疾病严重程度密切相关，因此可能通过增强ICAM-1表达促进红细胞或白细胞与内皮细胞的黏附。目前的观察结果进一步证明了细胞介导的免疫在人类脑型疟疾发病机制中的作用。
