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Recently several authors have reported that human neutrophils release neutrophil extracellular traps (NETs), which are protein-studded DNA matrices capable of trapping and killing pathogens. Here, we demonstrate that the leukotoxin (LKT) of\n                    <jats:italic>M. haemolytica<\/jats:italic>\n                    causes NET formation by bovine neutrophils in a CD18-dependent manner. Using an unacylated, noncytotoxic pro-LKT produced by an \u0394\n                    <jats:italic>lktC<\/jats:italic>\n                    mutant of\n                    <jats:italic>M. haemolytica<\/jats:italic>\n                    , we show that binding of unacylated pro-LKT stimulates NET formation despite a lack of cytotoxicity. Inhibition of LKT binding to the CD18 chain of lymphocyte function-associated antigen 1 (LFA-1) on bovine neutrophils reduced NET formation in response to LKT or\n                    <jats:italic>M. haemolytica<\/jats:italic>\n                    cells. Further investigation revealed that NETs formed in response to\n                    <jats:italic>M. haemolytica<\/jats:italic>\n                    are capable of trapping and killing a portion of the bacterial cells. NET formation was confirmed by confocal microscopy and by scanning and transmission electron microscopy. Prior exposure of bovine neutrophils to LKT enhanced subsequent trapping and killing of\n                    <jats:italic>M. haemolytica<\/jats:italic>\n                    cells in bovine NETs. Understanding NET formation in response to\n                    <jats:italic>M. haemolytica<\/jats:italic>\n                    and its LKT provides a new perspective on how neutrophils contribute to the pathogenesis of bovine respiratory disease.\n                  <\/jats:p>","DOI":"10.1128\/iai.00840-10","type":"journal-article","created":{"date-parts":[[2010,9,7]],"date-time":"2010-09-07T22:11:51Z","timestamp":1283897511000},"page":"4454-4466","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":76,"title":["<i>Mannheimia haemolytica<\/i>\n                    and Its Leukotoxin Cause Neutrophil Extracellular Trap Formation by Bovine Neutrophils"],"prefix":"10.1128","volume":"78","author":[{"given":"Nicole A.","family":"Aulik","sequence":"first","affiliation":[{"name":"Microbiology Doctoral Training Program"},{"name":"Department of Pathobiological Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrina M.","family":"Hellenbrand","sequence":"additional","affiliation":[{"name":"Department of Pathobiological Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Klos","sequence":"additional","affiliation":[{"name":"Department of Pathobiological Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles J.","family":"Czuprynski","sequence":"additional","affiliation":[{"name":"Microbiology Doctoral Training Program"},{"name":"Department of Pathobiological Sciences"},{"name":"Food Research Institute, University of Wisconsin\u2014Madison, Madison, Wisconsin 53706"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1177\/030098589403100307"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-009-0566-9"},{"key":"e_1_3_2_4_2","first-page":"161","volume":"179","year":"1999","unstructured":"Ambagala, T. 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