Yipp B G, Anand S, Schollaardt T, Patel K D, Looareesuwan S, Ho M
Department of Microbiology and Infectious Diseases, and the Immunology Research Group, University of Calgary, Alberta, Canada.
Blood. 2000 Sep 15;96(6):2292-8.
Plasmodium falciparum-infected erythrocytes (IRBCs) have been shown to interact with a number of endothelial adhesion molecules expressed on transfectants, on cell lines, and as immobilized purified receptor proteins under flow conditions. However, the experiments were designed in such a way that maximal numbers of adhesion molecules were provided as substratum. Whether the interactive events actually occur on microvascular endothelium, where the distribution and expression of adhesion molecules may be less, remains undetermined. In this study, the cytoadherance of IRBCs on human dermal microvascular endothelial cells (HDMECs) as a model of human microvasculature was examined. IRBCs were observed to tether, roll, and adhere on resting HDMECs, which constitutively expressed CD36 and intercellular adhesion molecule-1 (ICAM-1) at an optimal shear stress of 1 dyne/cm(2). Stimulation of HDMECs with tumor necrosis factor-alpha for 5 and 24 hours, which resulted in up-regulation of ICAM-1 and induction of vascular cell adhesion molecule-1 expression, significantly increased the percentage of rolling cells that adhered without affecting the rolling flux. In contrast, P-selectin expression on HDMECs induced by oncostatin M led to an increase in both rolling flux and adhesion. Inhibition studies with receptor-specific monoclonal antibodies revealed that adhesion of IRBCs on HDMECs was largely CD36 dependent, whereas rolling could be mediated by any of the adhesion molecules studied. Collectively, these findings indicate that IRBCs interact synergistically with multiple adhesion molecules on vascular endothelium. The rolling of IRBCs may be the rate-limiting step in cytoadherance, since it can be modulated by cytokines to enhance CD36-mediated IRBC adhesion.
恶性疟原虫感染的红细胞（IRBCs）已被证明在流动条件下可与转染细胞、细胞系上表达的多种内皮黏附分子以及固定化的纯化受体蛋白相互作用。然而，实验设计的方式是提供最大数量的黏附分子作为底物。而在微血管内皮上，黏附分子的分布和表达可能较少，这些相互作用事件是否真的发生在此处仍未确定。在本研究中，以人真皮微血管内皮细胞（HDMECs）作为人体微血管模型，检测了IRBCs的细胞黏附情况。观察到IRBCs在静息的HDMECs上拴系、滚动并黏附，这些HDMECs在1达因/平方厘米的最佳剪切应力下组成性表达CD36和细胞间黏附分子-1（ICAM-1）。用肿瘤坏死因子-α刺激HDMECs 5小时和24小时，导致ICAM-1上调并诱导血管细胞黏附分子-1表达，显著增加了黏附的滚动细胞百分比，而不影响滚动通量。相反，制瘤素M诱导HDMECs上P-选择素表达导致滚动通量和黏附均增加。用受体特异性单克隆抗体进行的抑制研究表明，IRBCs在HDMECs上的黏附很大程度上依赖于CD36，而滚动可由所研究的任何一种黏附分子介导。总体而言，这些发现表明IRBCs与血管内皮上的多种黏附分子协同相互作用。IRBCs的滚动可能是细胞黏附的限速步骤，因为它可被细胞因子调节以增强CD36介导的IRBC黏附。
