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
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)
Objectives—To determine effects of selectin inhibitor
TBC1269 on neutrophil infiltration, and neutrophilassociated
injury during pneumonia induced by
Mannheimia haemolytica and concentration of antimicrobial
anionic peptide (AAP) in bronchoalveolar
lavage fluid (BALF) as well as antimicrobial activity of
BALF from healthy (control) neonatal calves, neonatal
calves with M haemolytica-induced pneumonia,
neonatal calves with prior treatment with TBC1269,
and adult cattle.
Animals—Eighteen 1- to 3-day-old calves and 9 adult
Procedure—Calves were inoculated with M
haemolyticaor pyrogen-free saline (0.14M NaCl) solution
into the right cranial lung lobe, and BALF was collected
2 or 6 hours after inoculation. Thirty minutes
before and 2 hours after inoculation, 4 calves received
TBC1269. The BALF collected from 9 adult cattle was
used for comparison of BALF AAP concentration and
antimicrobial activity. Protein concentration and neutrophil
differential percentage and degeneration in
BALF were determined. An ELISA and killing assay
were used to determine BALF AAP concentration and
antimicrobial activity, respectively.
Results—Total protein concentration was significantly
decreased in BALF from calves receiving TBC1269.
Similar concentrations of AAP were detected in BALF
from all calves, which were 3-fold higher than those in
BALF from adult cattle. However, BALF from
neonates had little or no anti-M haemolytica activity.
Conclusions and Clinical Relevance—These results
suggest that TBC1269 decreases pulmonary tissue
injury in neonatal calves infected with M haemolytica.
Although AAP is detectable in neonatal BALF at 3
times the concentration detected in adult BALF,
neonatal BALF lacks antimicrobial activity for M
haemolytica. (Am J Vet Res 2001;62:665–672)