Integrin-EGF-3 domain of bovine CD18 is critical for Mannheimia haemolytica leukotoxin species-specific susceptibility.
Mannheimia haemolytica leukotoxin (LktA) is the primary virulence factor contributing to the pathogenesis of lung injury in bovine pneumonic pasteurellosis. Results from the authors' previous studies demonstrated that the site required for LktA binding leading to susceptibility to its biological effects resides within amino acid residues 500-600 of the extracellular region of bovine CD18. Experiments were designed to identify a much smaller functional domain within this 100 amino acid region of bovine CD18 that is critically required for species-specific susceptibility to LktA effects. Chimeric bovine X human CD18 with different integrin epidermal growth factor(I-EGF) like domains switched between bovine and human CD18 were generated and coexpressed with bovine CD11a in the human K562 cell line. The resulting chimeric transductants were tested for susceptibility to LktA-induced effects. The results demonstrate unequivocally that the I-EGF-3 domain of bovine CD18 (amino acid residues 541-581) is critical for conferring species-specific susceptibility to M. haemolytica leukotoxin.
Dileepan
Thamotharampillai
T
Department of Veterinary and Biomedical Sciences, University of Minnesota, St Paul, MN 55108, USA. mahes001@umn.edu
Kannan
Mathur S
MS
Walcheck
Bruce
B
Maheswaran
Samuel K
SK
D000595:Amino Acid Sequence; D000818:Animals; D001427:Bacterial Toxins / Q000633:toxicity*; D001665:Binding Sites; D018821:CD18 Antigens / Q000737:chemistry* / Q000235:genetics; D002417:Cattle; D002460:Cell Line; D005098:Exotoxins / Q000633:toxicity*; D006801:Humans; D016978:Mannheimia haemolytica / Q000472:pathogenicity*; D012766:Pasteurellosis, Pneumonic / Q000382:microbiology; D011993:Recombinant Fusion Proteins / Q000502:physiology; D013045:Species Specificity; D014774:Virulence
D001427:Bacterial Toxins; D018821:CD18 Antigens; D005098:Exotoxins; D011993:Recombinant Fusion Proteins; C018579:leukotoxin