Title: EFFECTS OF SYNTHETIC SELECTIN INHIBITOR, TBC1269, ON PARAMETERS OF TISSUE DAMAGE IN ACUTE P. HAEMOLYTICA PNEUMONIA IN CALVES
Radi, Z - IOWA STATE UNIV.,AMES, IA
Caverly, J - IOWA STATE UNIV.,AMES, IA
Dixon, R - TX BIOTECH, HOUSTON, TX.
Ackermann, M - IOWA STATE UNIV.,AMES, IA
Submitted to: American College of Veterinary Pathologists Abstracts
Publication Type: Abstract Only
Publication Acceptance Date: November 14, 1999
Publication Date: N/A
Tissue damage in bovine pulmonary pasteurellosis caused by P. haemolytica is due, in part, to neutrophil infiltration. We studied whether or not the in vivo inhibition of neutrophil adherence with a selectin inhibitor, TBC1269, would reduce the extent of pulmonary tissue damage as measured by conjugated diene analysis. The effects on apoptosis and nitric oxide synthase (NOS) levels were also measured. We inoculated 1- to 3-day-old colostrum-deprived Holstein calves intrabronchially with either P. haemolytica or pyrogen-free saline and necropsied the calves at either 2 or 6 hours post-inoculation (PI). One group of 6 hour-PI calves received the selectin inhibitor, (25 mg/kg, IV), 30 minutes prior to bacterial inoculation and 2 hours PI. The extent of tissue damage was significantly higher in the P. haemolytica-inoculated group at either 2 or 6 hours PI compared to the saline-inoculated calves. The TBC1269-treated calves had lower but not statistically significant tissue damage compared to the untreated calves. The TBC1269-treated calves had significantly higher apoptotic cell counts than the untreated calves. There was moderate to strong NOS staining in the normal calves. TBC1269-treated and -untreated calves had similar staining in unaffected regions and in cells adjacent to the inflammatory areas. Pneumonic areas had widespread weak NOS staining with strong staining of leukocytes. In conclusion, TBC1269 has potential therapeutic effects, but these protective effects are not complete. It may provide an important pathway for attenuating the detrimental aspects of the acute inflammatory process without eliminating the process entirely.