title: Human CD18 is the functional receptor for Aggregatibacter actinomycetemcomitans leukotoxin.
abstract: 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.
authors.affiliation: Department of Veterinary and Biomedical Sciences, University of Minnesota, 1971 Commonwealth Avenue, St. Paul, MN 55108, USA.
authors.forename: T
authors.initials: T
authors.lastname: Dileepan
authors.forename: S C
authors.initials: SC
authors.lastname: Kachlany
authors.forename: N V
authors.initials: NV
authors.lastname: Balashova
authors.forename: J
authors.initials: J
authors.lastname: Patel
authors.forename: S K
authors.initials: SK
authors.lastname: Maheswaran
mesh_terms: D016976:Aggregatibacter actinomycetemcomitans / Q000472:pathogenicity*; D020816:Amino Acid Motifs; D018821:CD18 Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D005098:Exotoxins / Q000378:metabolism* / Q000633:toxicity; D006801:Humans; D007962:Leukocytes / Q000382:microbiology; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity
chemical_list: D018821:CD18 Antigens; D005098:Exotoxins; D011993:Recombinant Fusion Proteins; C018579:leukotoxin