{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T10:06:13Z","timestamp":1760954773310},"reference-count":54,"publisher":"Cambridge University Press (CUP)","issue":"2","license":[{"start":{"date-parts":[[2007,2,28]],"date-time":"2007-02-28T00:00:00Z","timestamp":1172620800000},"content-version":"unspecified","delay-in-days":819,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":["www.cambridge.org"],"crossmark-restriction":true},"short-container-title":["Anim. Health. Res. Rev."],"published-print":{"date-parts":[[2004,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Progress in producing improved vaccines against bacterial diseases of cattle is limited by an incomplete understanding of the pathogenesis of these agents. Our group has been involved in investigations of two members of the family Pasteurellaceae,<jats:italic>Mannheimia haemolytica<\/jats:italic>and<jats:italic>Haemophilus somnus<\/jats:italic>, which illustrate some of the complexities that must be confronted. Susceptibility to<jats:italic>M. haemolytica<\/jats:italic>is greatly increased during active viral respiratory infection, resulting in rapid onset of a severe and even lethal pleuropneumonia. Despite years of investigation, understanding of the mechanisms underlying this viral\u2013bacterial synergism is incomplete. We have investigated the hypothesis that active viral infection increases the susceptibility of bovine leukocytes to the<jats:italic>M. haemolytica<\/jats:italic>leukotoxin by increasing the expression of or activating the \u03b2<jats:sub>2<\/jats:sub>integrin CD11a\/CD18 (LFA-1) on the leukocyte surface.<jats:italic>In vitro<\/jats:italic>exposure to proinflammatory cytokines (i.e. interleukin-1\u03b2, tumor necrosis factor-\u03b1 and interferon-\u03b3) increases LFA-1 expression on bovine leukocytes, which in turn correlates with increased binding and responsiveness to the leukotoxin. Alveolar macrophages and peripheral blood leukocytes from cattle with active bovine herpesvirus-1 (BVH-1) infection are more susceptible to the lethal effects of the leukotoxin<jats:italic>ex vivo<\/jats:italic>than leukocytes from uninfected cattle. Likewise,<jats:italic>in vitro<\/jats:italic>incubation of bovine leukocytes with bovine herpesvirus 1 (BHV-1) potentiates LFA-1 expression and makes the cells more responsive to leukotoxin. A striking characteristic of<jats:italic>H. somnus<\/jats:italic>infection is its propensity to cause vasculitis. We have shown that<jats:italic>H. somnus<\/jats:italic>and its lipo-oligosaccharide (LOS) trigger caspase activation and apoptosis in bovine endothelial cells<jats:italic>in vitro<\/jats:italic>. This effect is associated with the production of reactive oxygen and nitrogen intermediates, and is amplified in the presence of platelets. The adverse effects of<jats:italic>H. somnus<\/jats:italic>LOS are mediated in part by activation of endothelial cell purinergic receptors such as P2X<jats:sub>7<\/jats:sub>. Further dissection of the pathways that lead to endothelial cell damage in response to<jats:italic>H. somnus<\/jats:italic>might help in the development of new preventive or therapeutic regimens. A more thorough understanding of<jats:italic>M. haemolytica<\/jats:italic>and<jats:italic>H. somnus<\/jats:italic>virulence factors and their interactions with the host might identify new targets for prevention of bovine respiratory disease.<\/jats:p>","DOI":"10.1079\/ahr200483","type":"journal-article","created":{"date-parts":[[2005,7,4]],"date-time":"2005-07-04T01:41:09Z","timestamp":1120441269000},"page":"277-282","update-policy":"http:\/\/dx.doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":43,"title":["Complexities of the pathogenesis of<i>Mannheimia haemolytica<\/i>and<i>Haemophilus somnus<\/i>infections: challenges and potential opportunities for prevention?"],"prefix":"10.1017","volume":"5","author":[{"given":"Charles 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