Forsyth C B, Plow E F, Zhang L
The Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, The Cleveland Clinic Foundation, OH 44195, USA.
J Immunol. 1998 Dec 1;161(11):6198-205.
Interactions of microorganisms with integrins are central to the host defense mechanisms. The leukocyte integrin CD11b/CD18 is the principal adhesion receptor on leukocytes for Candida albicans, a major opportunistic pathogen. In this study we have investigated the roles of three regions within the receptor, the inserted (I) and lectin-like domains within the CD11b subunit, and the CD18 subunit, in CD11b/CD18-C. albicans interactions. We report four major findings. 1) A mutation in CD18 exerts a dominant negative effect on the function of the CD11b/CD18 complex. This interpretation is based on the observation that in the absence of CD18, the CD11b subunit alone binds C. albicans well, but a single point mutation at Ser138 of CD18 abolishes CD11b/CD18 binding of the fungus. 2) The lectin-like domain is not sufficient for CD11b/CD18-C. albicans interactions. Rather, the lectin-like domain appears to influence CD11b/CD18 binding activity by modulating the function of the I domain. 3) The I domain is the primary binding site for C. albicans in the receptor and is sufficient to support an efficient interaction. 4) We have identified specific amino acid sequences within the I domain that engage the microorganism. Compared with other ligands of CD11b/CD18, C. albicans has some unique as well as common contact sites within the I domain of the receptor. Such unique contact sites may underlie the ability of C. albicans to modulate CD11b/CD18 function and raise the possibility for selective interference of the microorganism-host leukocyte interactions.
微生物与整合素的相互作用是宿主防御机制的核心。白细胞整合素CD11b/CD18是白细胞上针对主要机会性病原体白色念珠菌的主要黏附受体。在本研究中，我们调查了该受体的三个区域，即CD11b亚基内的插入（I）结构域和凝集素样结构域，以及CD18亚基，在CD11b/CD18与白色念珠菌相互作用中的作用。我们报告了四项主要发现。1）CD18中的突变对CD11b/CD18复合物的功能产生显性负效应。这一解释基于以下观察结果：在没有CD18的情况下，单独的CD11b亚基能很好地结合白色念珠菌，但CD18的Ser138处的单点突变消除了真菌与CD11b/CD18的结合。2）凝集素样结构域不足以介导CD11b/CD18与白色念珠菌的相互作用。相反，凝集素样结构域似乎通过调节I结构域的功能来影响CD11b/CD18的结合活性。3）I结构域是受体中白色念珠菌的主要结合位点，足以支持高效的相互作用。4）我们已经确定了I结构域内与微生物结合的特定氨基酸序列。与CD11b/CD18的其他配体相比，白色念珠菌在受体的I结构域内有一些独特的以及共同的接触位点。这些独特的接触位点可能是白色念珠菌调节CD11b/CD18功能的能力的基础，并增加了选择性干扰微生物与宿主白细胞相互作用的可能性。
