Dileepan T, Kachlany S C, Balashova N V, Patel J, Maheswaran S K
Department of Veterinary and Biomedical Sciences, University of Minnesota, 1971 Commonwealth Avenue, St. Paul, MN 55108, USA.
Infect Immun. 2007 Oct;75(10):4851-6. doi: 10.1128/IAI.00314-07. Epub 2007 Jul 16.
Aggregatibacter (Actinobacillus) actinomycetemcomitans is the causative organism of localized aggressive periodontitis, a rapidly progressing degenerative disease of the gingival and periodontal ligaments, and is also implicated in causing subacute infective endocarditis in humans. The bacterium produces a variety of virulence factors, including an exotoxic leukotoxin (LtxA) that is a member of the repeats-in-toxin (RTX) family of bacterial cytolysins. LtxA exhibits a unique specificity to macrophages and polymorphonuclear cells of humans and other primates. Human lymphocyte function-associated antigen 1 (LFA-1) has been implicated as the putative receptor for LtxA. Human LFA-1 comprises the CD11a and CD18 subunits. It is not clear, however, which of its subunits serves as the functional receptor that confers species-specific susceptibility to LtxA. Here we demonstrate that the human CD18 is the receptor for LtxA based on experiments performed with chimeric beta2-integrins recombinantly expressed in a cell line that is resistant to LtxA effects. In addition, we show that the cysteine-rich tandem repeats encompassing integrin-epidermal growth factor-like domains 2, 3, and 4 of the extracellular region of human CD18 are critical for conferring susceptibility to LtxA-induced biological effects.
伴放线聚集杆菌（放线杆菌属）是局限性侵袭性牙周炎的致病微生物，这是一种牙龈和牙周韧带迅速进展的退行性疾病，并且也被认为可导致人类亚急性感染性心内膜炎。该细菌产生多种毒力因子，包括一种外毒素白细胞毒素（LtxA），它是细菌溶细胞素毒素重复序列（RTX）家族的成员。LtxA对人类和其他灵长类动物的巨噬细胞和多形核细胞表现出独特的特异性。人淋巴细胞功能相关抗原1（LFA-1）被认为是LtxA的假定受体。人LFA-1由CD11a和CD18亚基组成。然而，尚不清楚其哪个亚基作为功能性受体赋予对LtxA的物种特异性易感性。在此，我们基于在对LtxA效应具有抗性的细胞系中重组表达的嵌合β2整合素进行的实验，证明人CD18是LtxA的受体。此外，我们表明，人CD18细胞外区域包含整合素-表皮生长因子样结构域2、3和4的富含半胱氨酸的串联重复序列对于赋予对LtxA诱导的生物学效应的易感性至关重要。
