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间日疟原虫的一种受体:红细胞趋化因子受体。

A receptor for the malarial parasite Plasmodium vivax: the erythrocyte chemokine receptor.

作者信息

Horuk R, Chitnis C E, Darbonne W C, Colby T J, Rybicki A, Hadley T J, Miller L H

机构信息

Genentech, Inc., South San Francisco, CA 94080.

出版信息

Science. 1993 Aug 27;261(5125):1182-4. doi: 10.1126/science.7689250.

Abstract

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.

摘要

间日疟原虫和恶性疟原虫是人类疟疾的主要病因,但在撒哈拉以南非洲地区除外,该地区人群缺乏达菲血型抗原,而达菲血型抗原是间日疟原虫的红细胞受体。达菲阴性的人类红细胞对间日疟原虫及相关的猴疟原虫——诺氏疟原虫的入侵具有抗性。本研究中的多项证据表明,达菲血型抗原是趋化因子白细胞介素-8(IL-8)和黑素瘤生长刺激活性因子(MGSA)的红细胞受体。首先,IL-8与达菲阴性红细胞的结合极少。其次,一种针对达菲血型抗原的单克隆抗体可阻断IL-8和其他趋化因子与达菲阳性红细胞的结合。第三,MGSA和IL-8均可阻断寄生虫配体的结合以及诺氏疟原虫对人类红细胞的入侵,这提示了通过受体阻断进行抗疟治疗的可能性。

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