Mannheimia haemolytica leukotoxin-induced cytolysis of caprine (Capra hircus) leukocytes is mediated by the CD18 subunit of beta2-integrins

Mannheimiosis is the major respiratory disease among some ruminants, whereas it is not pathogenic for
other mammals, an observation that has been attributed to a specific interaction between Mannheimia
haemolytica leukotoxin (Lkt) and bovine or ovine CD18 subunit of lymphocyte function-associated
antigen-1 (LFA-1) and Mac-1. We therefore hypothesized that Lkt utilizes CD18 as its receptor on caprine
leukocytes as well. We have transiently transfected the b2-integrins-deficient K-562 cell line with cDNAs
encoding caprine CD11a and caprine CD18 to determine the susceptibility of the transfectants to Lktinduced
cytolysis. Flow cytometric analysis of the transfectants revealed surface expression of caprine
LFA-1 and lysis by Lkt in a concentration-dependent manner whereas the parent cells were not.
Moreover, K562 cells expressing caprine CD18 and human or bovine CD11a were also sensitive to Lkt
whereas K-562 cells expressing caprine CD11a and human CD18 were not. Taken together, these results
indicate that CD18 on caprine leukocytes serves as a receptor for Lkt.