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A Selectin Inhibitor Decreases Neutrophil Infiltration during Acute Mannheimia haemolytica Pneumonia

Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, IA (ZAR¹, JMG, MRA); Ruminant and Respiratory Diseases Unit, National Animal Disease Center, Agricultural Research Service—United States Department of Agriculture, Ames, IA (KAB); Texas Biotechnology Corporation, Houston, TX (RAD)

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.

Key words: Adhesion molecules; ICAM-1; Mannheimia haemolytica; selectins; shipping fever.

Request reprints from Dr. M. R. Ackermann, Department of Veterinary Pathology, 2738 Veterinary Medicine, Iowa State University, Ames, IA 50011-1250 (USA). E-mail: mackerma{at}iastate.edu.

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