{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T08:29:54Z","timestamp":1759048194502,"version":"3.38.0"},"reference-count":38,"publisher":"American Veterinary Medical Association (AVMA)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ajvr"],"published-print":{"date-parts":[[2000,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n\t\t\t\t<jats:p>\n\t\t\t\t\t<jats:bold>Objective<\/jats:bold>\u2014To characterize ultrastructural changes of\nbovine lymphocytes exposed to <jats:italic>Pasteurella haemolytica<\/jats:italic>\nleukotoxin (LKT).<\/jats:p>\n\t\t\t\t<jats:p>\n\t\t\t\t\t<jats:bold>Sample Population<\/jats:bold>\u2014Partially purified LKT from a wild\ntype <jats:italic>P haemolytica<\/jats:italic> A1 strain and inactive pro-LKT from\nan isogeneic mutant <jats:italic>P haemolytica<\/jats:italic> strain. Isolated bovine\nlymphocytes were obtained from 2 healthy calves.<\/jats:p>\n\t\t\t\t<jats:p>\n\t\t\t\t\t<jats:bold>Procedure<\/jats:bold>\u2014Isolated bovine lymphocytes were incubated\nwith various concentrations of LKT and pro-LKT\nfor 3 hours at 37 C and examined by use of transmission\nelectron microscopy. A cytochemical Klenow\nDNA fragmentation assay was used to examine lymphocytes\nfor DNA fragmentation.<\/jats:p>\n\t\t\t\t<jats:p>\n\t\t\t\t\t<jats:bold>Results<\/jats:bold>\u2014Lymphocytes incubated with LKT at a high\nconcentration (1.0 toxic U\/ml) had ultrastructural evidence\nof cytoplasmic and nuclear membrane rupture\nand swelling or lysis of mitochondria. Low concentrations\nof leukotoxin (0.1 toxic U\/ml) induced DNA\nfragmentation in 80% of lymphocytes. Ultrastructurally,\nthese cells had nuclear membrane blebbing,\ncytoplasmic vaculation, chromatin condensation,\nnuclear fragmentation, and membrane-bound\napoptotic bodies. Incubation of lymphocytes with\nLKT at extremely low concentrations (0.001 toxic\nU\/ml) or with pro-LKT did not alter their ultrastructure.\nInclusion of 0.5 m<jats:italic>M<\/jats:italic> ZnCl<jats:sub>2<\/jats:sub>\nin the medium\nblocked leukotoxin-induced ultrastructural changes in\nbovine lymphocytes.<\/jats:p>\n\t\t\t\t<jats:p>\n\t\t\t\t\t<jats:bold>Conclusions and Clinical Relevance<\/jats:bold>\u2014Low concentrations\nof LKT induce apoptosis and high concentrations\ninduce oncotic cell lysis in bovine lymphocytes.\nThe ability of low LKT concentrations to induce apoptosis\nin host leukocytes may allow bacteria to escape\nhost immune surveillance and colonize the host.\n(<jats:italic>Am J Vet Res<\/jats:italic> 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