Effects of the synthetic selectin inhibitor TBC1269 on tissue damage during acute Mannheimia haemolytica-induced pneumonia in neonatal calves

dc.contributor.author Radi, Zaher
dc.contributor.author Caverly, Jessica
dc.contributor.author Ackermann, Mark
dc.contributor.author Dixon, Richard
dc.contributor.author Brogden, Kim
dc.contributor.author Ackermann, Mark
dc.contributor.department Veterinary Pathology
dc.date 2018-02-13T06:27:01.000
dc.date.accessioned 2020-07-07T05:15:55Z
dc.date.available 2020-07-07T05:15:55Z
dc.date.embargo 2013-02-26
dc.date.issued 2001-01-01
dc.description.abstract <p><strong>Objective</strong>—To determine effects of the selectin inhibitor TBC1269 on neutrophil-mediated pulmonary damage during acute <em>Mannheimia haemolytica-induced</em>pneumonia in newborn calves.</p> <p><strong>Animals</strong>—Eighteen 1- to 3-day-old colostrumdeprived calves.</p> <p><strong>Procedure</strong>—<em>Mannheimia haemolytica</em> or saline (0.9% NaCl) solution was inoculated in both cranial lung lobes of 12 and 6 calves, respectively. Calves were euthanatized 2 (saline, n = 3; <em>M haemolytica</em>, n = 4) or 6 hours (saline, n = 3; <em>M haemolytica</em>, n = 8) after inoculation. Four <em>M haemolytica</em>-inoculated calves euthanatized at 6 hours also received TBC1269 (25 mg/kg, IV) 30 minutes before and 2 hours after inoculation. Conjugated diene (CD) concentrations, inducible nitric oxide synthase (iNOS) expression, and apoptotic cell counts were determined in lung specimens collected during necropsy.</p> <p><strong>Results</strong>—Conjugated diene concentrations were significantly increased in all <em>M haemolytica</em>-inoculated groups, compared with saline-inoculated groups. Calves treated with TBC1269 had decreased concentrations of CD, compared with untreated calves, although the difference was not significant. Number of apoptotic neutrophils and macrophages increased significantly in TBC1269-treated calves, compared with untreated calves. Inducible nitric oxide synthase was expressed by epithelial cells and leukocytes. However, iNOS was less abundant in airway epithelial cells associated with inflammatory exudates. Degree of iNOS expression was similar between TBC1269-treated and untreated calves.</p> <p><strong>Conclusions</strong>—<em>Mannheimia haemolytica</em> infection in neonatal calves resulted in pulmonary tissue damage and decreased epithelial cell iNOS expression. The selectin inhibitor TCB1269 altered, but did not completely inhibit, neutrophil-mediated pulmonary damage.</p>
dc.description.comments <p>This article is from <em>American Journal of Veterinary Research </em>62, no. 1 (January 2001): 17–22, doi:<a href="http://dx.doi.org/10.2460/ajvr.2001.62.17" target="_blank">10.2460/ajvr.2001.62.17</a>.</p>
dc.format.mimetype application/pdf
dc.identifier archive/lib.dr.iastate.edu/vpath_pubs/44/
dc.identifier.articleid 1044
dc.identifier.contextkey 3793642
dc.identifier.s3bucket isulib-bepress-aws-west
dc.identifier.submissionpath vpath_pubs/44
dc.identifier.uri https://dr.lib.iastate.edu/handle/20.500.12876/92469
dc.language.iso en
dc.source.bitstream archive/lib.dr.iastate.edu/vpath_pubs/44/2001_Radi_EffectsSyntheticSelectin.pdf|||Sat Jan 15 00:17:01 UTC 2022
dc.source.uri 10.2460/ajvr.2001.62.17
dc.subject.disciplines Veterinary Pathology and Pathobiology
dc.title Effects of the synthetic selectin inhibitor TBC1269 on tissue damage during acute Mannheimia haemolytica-induced pneumonia in neonatal calves
dc.type article
dc.type.genre article
dspace.entity.type Publication
relation.isAuthorOfPublication 86c1ed73-b60d-48ce-8f35-449bc320a693
relation.isOrgUnitOfPublication cf38d7e3-b5f8-4859-83e3-ae8fab6a4c5f
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