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 neutrophil-mediated pulmonary damage during acute Mannheimia haemolytica-induced pneumonia in newborn calves.


METHODS
Eighteen 1- to 3-day-old colostrum-deprived calves.


METHODS
Mannheimia haemolytica 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; M haemolytica, n = 4) or 6 hours (saline, n = 3; M haemolytica, n = 8) after inoculation. Four M haemolytica-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.


RESULTS
Conjugated diene concentrations were significantly increased in all M haemolytica-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 inTBC1269-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.


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, neutrophil-mediated pulmonary damage.
Radi
Z A
ZA
Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames 50011, USA.
Caverly
J M
JM
Dixon
R A
RA
Brogden
K A
KA
Ackermann
M R
MR
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D002417:Cattle; D004847:Epithelial Cells / Q000201:enzymology; D007962:Leukocytes / Q000201:enzymology; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008358:Mannose / Q000031:analogs & derivatives; D008362:Mannosides / Q000627:therapeutic use*; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D015661:Pasteurellaceae; D012766:Pasteurellosis, Pneumonic / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D019087:Selectins / Q000502:physiology
D001713:Biphenyl Compounds; D008362:Mannosides; D019087:Selectins; C108700:bimosiamose disodium; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D008358:Mannose