{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T02:53:49Z","timestamp":1781664829575,"version":"3.54.5"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2007,10,1]],"date-time":"2007-10-01T00:00:00Z","timestamp":1191196800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2007,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The ruminant-specific leukotoxin (Lkt) of<jats:italic>Mannheimia haemolytica<\/jats:italic>is the key virulence factor contributing to the pathogenesis of lung injury in bovine pneumonic pasteurellosis. Previous studies by us and others indicate that<jats:italic>M. haemolytica<\/jats:italic>Lkt binds to CD18, the \u03b2 subunit of bovine \u03b2<jats:sub>2<\/jats:sub>-integrins on leukocytes, and that the species specificity of Lkt-induced effects is resident in the \u03b2 subunit CD18 and not in the \u03b1 subunit CD11. However, Lkt also binds to the CD11a subunit of LFA-1. Furthermore, antibodies specific for CD18 or CD11a inhibit signaling events leading to elevation of intracellular [Ca<jats:sup>2+<\/jats:sup>], tyrosine phosphorylation of the cytosolic domain of CD18, and cytolysis of bovine leukocytes. These observations underscore the need for further investigation to identify the precise subunit of bovine LFA-1 utilized by<jats:italic>M. haemolytica<\/jats:italic>Lkt as the functional receptor. For this purpose, monomeric bovine CD18 and CD11a and heterodimeric LFA-1 were expressed in the HEK-293 cell line by transfection, and the resulting transfectants were tested for susceptibility to Lkt-induced effects. All three transfectants effectively bound Lkt. However, Lkt-induced cytolysis was observed only with transfectants expressing monomeric bovine CD18 or LFA-1. Furthermore, intracellular [Ca<jats:sup>2+<\/jats:sup>] elevation following exposure to Lkt, which is a marker for postbinding signaling leading to cellular activation, was seen only with transfectants expressing monomeric bovine CD18 or LFA-1. These results clearly indicate that the bovine CD18 subunit of \u03b2<jats:sub>2<\/jats:sub>-integrins is the functional receptor for<jats:italic>M. haemolytica<\/jats:italic>Lkt.<\/jats:p>","DOI":"10.1128\/iai.00808-07","type":"journal-article","created":{"date-parts":[[2007,8,14]],"date-time":"2007-08-14T00:26:09Z","timestamp":1187051169000},"page":"5004-5010","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":35,"title":["Monomeric Expression of Bovine \u03b2<sub>2<\/sub>-Integrin Subunits Reveals Their Role in<i>Mannheimia haemolytica<\/i>Leukotoxin-Induced Biological Effects"],"prefix":"10.1128","volume":"75","author":[{"given":"Rohana P.","family":"Dassanayake","sequence":"first","affiliation":[{"name":"Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington 99164-7040"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel K.","family":"Maheswaran","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, Minnesota 55108"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subramaniam","family":"Srikumaran","sequence":"additional","affiliation":[{"name":"Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington 99164-7040"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"161","volume":"179","year":"1999","unstructured":"Ambagala, T. 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