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Broad-spectrum activity against bacterial mastitis pathogens and activation of mammary epithelial cells support a protective role of neutrophil cathelicidins in bovine mastitis.

Abstract
Cathelicidins are peptide components of the innate immune system of mammals. Apart from exerting a direct antibiotic activity, they can also trigger specific defense responses in the host. Their roles in various pathophysiological conditions have been studied, but there is a lack of published information on their expression and activities in the context of mastitis. The aims of this study were to investigate the expression of the bovine cathelicidins BMAP-27, BMAP-28, Bac5, and indolicidin in healthy and infected mammary tissue and in lipopolysaccharide (LPS)-treated cells, to determine their activities against bacteria isolated from bovine mastitis, and to examine their potentials to trigger defense responses in bovine mammary cells. The genes were found to be upregulated in LPS-stimulated neutrophils, but not in infected quarters or epithelial cells. All peptides showed a variably broad spectrum of activity against 28 bacterial isolates from bovine mastitis (MIC values, 0.5 to 32 microM), some of which were antibiotic resistant. The activity of each peptide was significantly enhanced when it was pairwise tested with the other peptides, reaching the synergy threshold when indolicidin was present. The bactericidal activity was sensitive to milk components; BMAP-27 and -28 were highly effective in mastitic bovine milk and inhibited in milk from healthy cows. Both peptides were also active in whey and in blood serum and triggered the expression of tumor necrosis factor alpha (TNF-alpha) in bovine mammary epithelial cells. Our results indicate multiple roles for the bovine cathelicidins in mastitis, with complementary and mutually enhanced antimicrobial activities against causative pathogens and the capacity to activate host cells.
AuthorsLinda Tomasinsig, Gennyfer De Conti, Barbara Skerlavaj, Renata Piccinini, Maria Mazzilli, Francesca D'Este, Alessandro Tossi, Margherita Zanetti
JournalInfection and immunity (Infect Immun) Vol. 78 Issue 4 Pg. 1781-8 (Apr 2010) ISSN: 1098-5522 [Electronic] United States
PMID20100862 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-Bacterial Agents
  • Antimicrobial Cationic Peptides
  • Cathelicidins
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • indolicidin
Topics
  • Animals
  • Anti-Bacterial Agents (immunology, pharmacology)
  • Antimicrobial Cationic Peptides (biosynthesis, immunology, pharmacology)
  • Bacteria (drug effects, immunology)
  • Cathelicidins (biosynthesis, immunology, pharmacology)
  • Cattle
  • Cells, Cultured
  • Drug Synergism
  • Epithelial Cells (immunology)
  • Female
  • Gene Expression Profiling
  • Lipopolysaccharides (immunology)
  • Mammary Glands, Animal (immunology, microbiology, pathology)
  • Mastitis, Bovine (immunology)
  • Microbial Sensitivity Tests
  • Microbial Viability (drug effects)
  • Neutrophils (immunology)
  • Tumor Necrosis Factor-alpha (metabolism)
  • Up-Regulation

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