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Title: EFFECTS OF A SYNTHETIC SELECTIN INHIBITOR, TBC1269, ON PARAMETERS OF TISSUE DAMAGE IN ACUTE PASTEURELLA HAEMOLYTICA PNEUMONIA

Author
item RADI, ZAHR - IA STATE UNIV., AMES, IA
item CAVERLY, JESSICA - IA STATE UNIV., AMES, IA
item DIXON, RICHARD - TX BIOTECH. CORP. HOUSTON
item Brogden, Kim
item ACKERMANN, MARK - IA STATE UNIV., AMES, IA

Submitted to: American Journal of Veterinary Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/21/2000
Publication Date: N/A
Citation: 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 leading to the development of pneumonia are known by scientists and veterinarians. As part of our ongoing studies to understand the disease process, we assessed the role of selectins in the pathogenesis of pneumonia. Selectins mediate initial leukocyte adherence to vascular endothelial cells, and reactive- oxygen intermediates released from infiltrating leukocytes are known to cause tissue damage. We investigated the protective effects of selectin inhibition using a new selectin inhibitor, TBC1269 in a calf model during acute pneumonia. Overall, TBC1269 was found to alter programmed cell death hof leukocytes. It may provide an important pathway for attenuating the detrimental aspects of the acute inflammatory process without eliminating the process entirely. Corollary benefits of this research 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: Selectins (E-, L-, and P-selectin) mediate initial leukocyte adherence to vascular endothelial cells, and reactive-oxygen intermediates (ROI) released from infiltrating leukocytes are known to cause tissue damage. We investigated the in vivo protective effects of selectin inhibition using a new selectin inhibitor, TBC1269. Calves were inoculated intrabronchially with Pasteurella haemolytica and injected intravenously with TBC1269. The interactive role of conjugated dienes (CD), programmed cell death (PCD), and inducible nitric oxide (iNOS) during neutrophil-mediated injury and in TBC1269 treatment was assessed. Levels of CD I lung tissues significantly increased after P. haemolytica inoculation. TBC1269 treatment decreased levels of CD in the lung. A significant increase in PCD of leukocytes was observed in the TBC1269-treated compared with the untreated calves. The iNOS expression was similar between treated and non-treated calves. iNOS was decreased in areas where airway epithelial cells were associated with abundant inflammatory exudate. Overall, TBC1269 alters PCD actively in vivo. It may provide an important pathway for attenuating the detrimental aspects of the acute inflammatory process without eliminating the process entirely.