Objective—To determine effects of the selectin
inhibitor TBC1269 on neutrophil-mediated pulmonary
damage during acute Mannheimia haemolytica-induced pneumonia
in newborn calves.
Animals—Eighteen 1- to 3-day-old colostrumdeprived
calves.
Procedure—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 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.
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.
( Am J Vet Res 2001;62:17–22)