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

Objective-To determine effects of the selectin inhibitor TBC1269 on neutrop hil-mediated pulmonary damage during acute Mannheimia haemolytica-induced p neumonia in newborn calves. Animals-Eighteen 1- to 3-day-old colostrum-deprived calves. Procedure-Mannheimia haemolytica or saline (0.9% NaCl) solution was inocula ted in both cranial lung lobes of 12 and 6 calves, respectively. Calves wer e euthanatized 2 (saline, n = 3; M haemolytica, n = 4) or 6 hours (saline, n = 3; M haemolytica, n = 8) after inoculation. Four M haemolytica-inoculat ed calves euthanatized at 6 hours also received TBC1269 (25 mg/kg, IV) 30 m inutes before and 2 hours after inoculation. Conjugated diene (CD) concentr ations, inducible nitric oxide synthase (iNOS) expression, and apoptotic ce ll counts were determined in lung specimens collected during necropsy. Results-Conjugated diene concentrations were significantly increased in all M haemolytica-inoculated groups, compared with saline-inoculated groups. C arves treated with TBC1269 had decreased concentrations of CD, compared wit h untreated calves, although the difference was not significant. Number of apoptotic neutrophils and macrophages increased significantly in TBC1269-tr eated carves, compared with untreated calves, Inducible nitric oxide syntha se 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 untreate d calves. Conclusions-Mannheimia haemolytica 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, neutro phil-mediated pulmonary damage.