Submitted to: American Journal of Veterinary Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/16/2001
Publication Date: N/A
Interpretive Summary: Respiratory tract diseases are a leading cause of loss from disease in the cattle, sheep and goat industries. Annual loss in the United States is estimated to exceed one billion dollars. Losses are from mortality, reduced feed efficiency, and slaughter condemnations, as well as prevention and treatment measures. Currently, not all the factors involved in natural linnate immunity are known by scientists and veterinarians. As part of our ongoing studies to identify mechanisms leading to neutrophil infiltration and innate antimicrobial peptides, we found that TBC 1269 inhibits neutrophil infiltration and protein exudation into the lungs of neonatal calves infected with M. haemolytica, and that while antimicrobial anionic peptide is present in neonatal bovine lung, it lacks significant antimicrobial activity to M. haemolytica. This observation suggests that anionic peptides are present in lung cells, and fluid of cattle may not provide much innate pulmonary protection against infection when animals ar young. This would be an important factor in preventing or treating shipping fever of cattle. Corollary benefits include an increase in the profitability and international competitiveness of the U. S. cattle industry, a stronger rural economy, and a continued supply of inexpensive, wholesome beef and beef products for the American consumer.
Technical Abstract: Respiratory tract diseases are a leading cause of loss from disease in the cattle, sheep and goat industries. Currently, not all the factors involved in natural innate immunity are known. In this study, we wanted to determine (i) whether inhibition of neutrophil adherence with selectin inhibitor TBC 1269 would reduce neutrophil infiltration and neutrophil- associated injury during Mannheimia haemolytica pneumonia, and (ii) the concentration and activity of anionic peptide (AP) in bronchoalveolar lavage fluid (BALF) of saline- and M. haemolytica-inoculated neonatal calves. To show this, eighteen 1- to 3-day-old, colostrum-deprived calves were inoculated with either M. haemolytica or saline by fiberoptic bronchoscopy into the right cranial lung lobe. At 2 or 6 hours post- inoculation (PI), BALF was collected. Four calves (6 hours PI) received selectin inhibitor TBC 1269. BALF from nine cattle was used for comparison nof AP. The amount of neutrophils, protein, and AP were assessed. Lower neutrophil scores and decreased total protein were found in BALF from calves receiving selectin inhibitor TBC 1269. AP was present in BALF from all control and experimental neonates at statistically similar concentrations that were three fold higher than those found in BALF from adult animals. However, BALF of neonates had little to no anti-M. haemolytica activity when compared to BALF of adult cattle. These results suggest (i) that TBC 1269 inhibits neutrophil infiltration and protein exudation into the lungs of neonatal calves infected with M. haemolytica, and (ii) that while AP is present in neonatal bovine lung, it lacks significant antimicrobial activity to M. haemolytica.