Comparison of bronchoalveolar lavage fluid obtained from Mannheimia haemolytica-inoculated calves with and without prior treatment with the selectin inhibitor TBC1269

Jessica M. Caverly Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, IA 50011-1250.

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Zaher A. Radi Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, IA 50011-1250
Present address is Department of Biomedical Science and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061-0442.

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Claire B. Andreasen Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, IA 50011-1250.

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Richard A. F. Dixon Texas Biotechnology Corporation, 7000 Fannin, Houston, TX 77030.

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Kim A. Brogden Respiratory Diseases of Livestock Research Unit, USDA-Agriculture Research Service, National Animal Disease Center, Ames, IA 50010.

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Mark R. Ackermann Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, IA 50011-1250.

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Abstract

Objectives—To determine effects of selectin inhibitor TBC1269 on neutrophil infiltration, and neutrophilassociated 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.

Animals—Eighteen 1- to 3-day-old calves and 9 adult cattle.

Procedure—Calves were inoculated with M haemolyticaor 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 and Clinical Relevance—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. (Am J Vet Res 2001;62:665–672)

Abstract

Objectives—To determine effects of selectin inhibitor TBC1269 on neutrophil infiltration, and neutrophilassociated 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.

Animals—Eighteen 1- to 3-day-old calves and 9 adult cattle.

Procedure—Calves were inoculated with M haemolyticaor 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 and Clinical Relevance—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. (Am J Vet Res 2001;62:665–672)

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