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Title: A SELECTIN INHIBITOR DECREASES NEUTROPHIL INFILTRATION DURING ACUTE MANNHEIMIA HAEMOLYTICA PNEUMONIA

Author
item RADI, Z - IA STATE UNIV., AMES, IA
item BROGDEN, KIM
item DIXON, R - IA STATE UNIV., AMES, IA
item GALLUP, J - IA STATE UNIV., AMES, IA
item ACKERMANN, MARK - IA STATE UNIV., AMES, IA

Submitted to: Veterinary Pathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/20/2002
Publication Date: 11/20/2002
Citation: RADI, Z.A., BROGDEN, K.A., DIXON, R.A., GALLUP, J.M., ACKERMANN, M.R. A SELECTIN INHIBITOR DECREASES NEUTROPHIL INFILTRATION DURING ACUTE MANNHEIMIA HAEMOLYTICA PNEUMONIA. VETERINARY PATHOLOGY. 2002. v. 39(6). p. 697-705.

Interpretive Summary: Respiratory tract diseases are a leading cause of loss from disease in the cattle industry. Currently, not all the factors preventing infectious disease in normal animals are known. As part of our ongoing studies to understand the pathogenesis of pneumonia, we assessed the effect of selectin inhibitor on neutrophil infiltration during acute Mannheimia haemolytica infection. Neonatal calves were inoculated intrabronchially with Mannheimia (Pasteurella) haemolytica, and lung tissue was collected 2 and 6 hours later. At 6 hours, one group inoculated with M. haemolytica received TBC1269 intravenously before and after inoculation and one group did not. Significantly fewer neutrophils (P < 0.05) were present in the alveolar lumen and septae, and the bronchiolar lumen and lamina propria in the lungs of TBC1269-treated calves compared with untreated calves at 6 hours PI. This work suggests that during acute pneumonia of neonates 1) neutrophil infiltrates progressively increase in the alveolar lumens and septae but decrease in the bronchial lumen and epithelium with time, 2) TBC1269 reduces neutrophil infiltration into specific regions of alveoli and bronchioles rather than uniformly throughout the lung, and 3) selectin inhibition does not affect the location and intensity of ICAM-1 expression. On the basis of our findings, it appears that this would be an important factor in preventing infection and averting the disease process.

Technical Abstract: The degree to which the selectin inhibitor TBC1269 reduces neutrophil infiltration in specific microscopic locations of the lung during acute pneumonia of neonates was determined. Neonatal calves were inoculated intrabronchially with Mannheimia (Pasteurella) haemolytica or saline, and lung tissue was collected at 2 and 6 hours postinoculation (PI). One 6-hour group inoculated with M. haemolytica received TBC1269 intravenously before and after inoculation with M. haemolytica. Infiltrates of neutrophils were significantly higher in the alveolar lumen and septae but lower in the bronchial lumen and epithelium at 6 hours PI than at 2 hours PI. Significantly fewer neutrophils (P < 0.05) were present in the alveolar lumen and septae, and the bronchiolar lumen and lamina propria in the lungs of TBC1269-treated calves compared with untreated calves at 6 hours PI. TBC1269 did not alter the infiltration into bronchi and blood vessels or the expression of the selectin-independent adhesion molecule, ICAM-1. This work suggests that during acute pneumonia of neonates 1) neutrophil infiltrates progressively increase in the alveolar lumens and septae but decrease in the bronchial lumen and epithelium with time, 2) TBC1269 reduces neutrophil infiltration into specific regions of alveoli and bronchioles rather than uniformly throughout the lung, and 3) selectin inhibition does not affect the location and intensity of ICAM-1 expression.