title: Comparison of bronchoalveolar lavage fluid obtained from Mannheimia haemolytica-inoculated calves with and without prior treatment with the selectin inhibitor TBC1269.
abstract: OBJECTIVE
  To determine effects of selectin inhibitor TBC1269 on neutrophil infiltration, and neutrophil-associated injury during pneumonia induced by Mannheimia haemolytica and concentration of antimicrobial anionic peptide (AAP) in bronchoalveolar lavage fluid (BALF) as well as antimicrobial activity of BALF from healthy (control) neonatal calves, neonatal calves with M haemolytica-induced pneumonia, neonatal calves with prior treatment with TBC1269, and adult cattle.
  
  
  METHODS
  Eighteen 1- to 3-day-old calves and 9 adult cattle.
  
  
  METHODS
  Calves were inoculated with M haemolytica or pyrogen-free saline (0.14M NaCl) solution into the right cranial lung lobe, and BALF was collected 2 or 6 hours after inoculation. Thirty minutes before and 2 hours after inoculation, 4 calves received TBC1269. The BALF collected from 9 adult cattle was used for comparison of BALF AAP concentration and antimicrobial activity. Protein concentration and neutrophil differential percentage and degeneration in BALF were determined. An ELISA and killing assay were used to determine BALF AAP concentration and antimicrobial activity, respectively.
  
  
  RESULTS
  Total protein concentration was significantly decreased in BALF from calves receiving TBC1269. Similar concentrations of AAP were detected in BALF from all calves, which were 3-fold higher than those in BALF from adult cattle. However, BALF from neonates had little or no anti-M haemolytica activity.
  
  
  CONCLUSIONS
  These results suggest that TBC1269 decreases pulmonary tissue injury in neonatal calves infected with M haemolytica. Although AAP is detectable in neonatal BALF at 3 times the concentration detected in adult BALF, neonatal BALF lacks antimicrobial activity for M haemolytica.
authors.affiliation: Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames 50011-1250, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Caverly
authors.forename: Z A
authors.initials: ZA
authors.lastname: Radi
authors.forename: C B
authors.initials: CB
authors.lastname: Andreasen
authors.forename: R A
authors.initials: RA
authors.lastname: Dixon
authors.forename: K A
authors.initials: KA
authors.lastname: Brogden
authors.forename: M R
authors.initials: MR
authors.lastname: Ackermann
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D002417:Cattle; D002418:Cattle Diseases / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology*; D002448:Cell Adhesion / Q000187:drug effects; D008297:Male; D016978:Mannheimia haemolytica; D008358:Mannose / Q000031:analogs & derivatives; D008362:Mannosides / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D010326:Pasteurella Infections / Q000188:drug therapy / Q000276:immunology / Q000662:veterinary*; D010455:Peptides / Q000378:metabolism; D018410:Pneumonia, Bacterial / Q000188:drug therapy / Q000382:microbiology / Q000662:veterinary*
chemical_list: D018927:Anti-Asthmatic Agents; D001713:Biphenyl Compounds; D008362:Mannosides; D010455:Peptides; C108700:bimosiamose disodium; D008358:Mannose