A RECEPTOR FOR THE MALARIAL PARASITE PLASMODIUM-VIVAX - THE ERYTHROCYTE CHEMOKINE RECEPTOR
A RECEPTOR FOR THE MALARIAL PARASITE PLASMODIUM-VIVAX - THE ERYTHROCYTE CHEMOKINE RECEPTOR
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DOI：
10.1126/science.7689250
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发表时间：
1993-08-27
期刊：
影响因子：
56.9
通讯作者：
MILLER, LH
中科院分区：
文献类型：
--
作者：
HORUK, R;CHITNIS, CE;MILLER, LH
间日疟原虫和恶性疟原虫是人类疟疾的主要原因，除了在撒哈拉以南非洲，那里的人们缺乏达菲血型抗原，即间日疟原虫的红细胞受体。Duffy阴性人红细胞对间日疟原虫和相关猴疟疾诺氏疟原虫的侵袭具有抗性。本研究中的几条证据表明，Duffy血型抗原是趋化因子白细胞介素-8（IL-8）和黑色素瘤生长刺激活性（MGSA）的红细胞受体。首先，IL-8与Duffy阴性红细胞的结合最低。第二，Duffy血型抗原的单克隆抗体阻断了IL-8和其他趋化因子与Duffy阳性红细胞的结合。第三，MGSA和IL-8都阻断了诺氏疟原虫与疟原虫配体的结合和诺氏疟原虫对人红细胞的侵袭，这表明受体阻断剂用于抗疟疾治疗的可能性。
Plasmodium vivax and P. falciparum are the major causes of human malaria, except in sub-Saharan Africa where people lack the Duffy blood group antigen, the erythrocyte receptor for P. vivax. Duffy negative human erythrocytes are resistant to invasion by P. vivax and the related monkey malaria, P. knowlesi. Several lines of evidence in the present study indicate that the Duffy blood group antigen is the erythrocyte receptor for the chemokines interleukin-8 (IL-8) and melanoma growth stimulatory activity (MGSA). First, IL-8 binds minimally to Duffy negative erythrocytes. Second, a monoclonal antibody to the Duffy blood group antigen blocked binding of IL-8 and other chemokines to Duffy positive erythrocytes. Third, both MGSA and IL-8 blocked the binding of the parasite ligand and the invasion of human erythrocytes by P. knowlesi, suggesting the possibility of receptor blockade for anti-malarial therapy.