ANIONIC ANTIMICROBIAL PEPTIDE-LYSOZYME INTERACTIONS IN INNATE PULMONARY IMMUNITY

Authors: KALFA, V - VISITING SCI.,TURKEY; BROGDEN, KIM

Submitted to: International Journal of Antimicrobial Agents
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/24/1999
Publication Date: N/A
Citation: N/A

Interpretive Summary: Respiratory tract diseases are a leading cause of loss from disease in the cattle, sheep and goat industries. Annual loss in the United States is estimated to exceed one billion dollars. Losses are from mortality, reduced feed efficiency, and slaughter condemnations, as well as prevention and treatment measures. Currently, not all the factors involved in natural limmunity are known by scientists and veterinarians. The respiratory tract contains numerous natural antimicrobial factors necessary for normal pulmonary defense. Despite differences in concentration, size, mechanism of action, and electric charge, many of these molecules are thought to reside in airway surface liquid simultaneously. However, little information exists on the interactions affecting antimicrobial activity. In this study, we found that lysozyme and anionic antimicrobial peptide appear not to significantly interact at physiologically relevant concentrations, but work independently of each other. These results help define interactions necessary for effective natural immunity that if lost, might increase the susceptibility of animals to pneumonia. These findings may lead to the development of prophylactic treatments that could increase the resistance of cattle to shipping fever pneumonia. Corollary benefits include an increase in the profitability and international competitiveness of the U. S. cattle industry, a stronger rural economy, and a continued supply of inexpensive, wholesome beef, and beef products for the American consumer.

Technical Abstract: The respiratory tract contains numerous antimicrobial factors necessary for normal innate pulmonary defense. Although many of these molecules are thought to reside in airway surface liquid (ASL) simultaneously, little information exists concerning antimicrobial peptide antagonistic, additive, or synergistic interactions. Since both cationic lysozyme and AP are found din high concentrations in ASL, the purpose of this study was to assess any interaction that may affect antimicrobial activity. For this, P. haemolytica, M. lysodeikticus, or P. aeruginosa (500 CFU) were added to egg white lysozyme (250 to 3.91 ug /ml) or human neutrophil lysozyme (50 to 0.78 ug /ml) and H-GADDDDD-OH (from 0.5 to 0.01 mM) mixtures in 50, 100, or 150 mM NaCl; incubated for 2 hours; and then plated. In this assay, the MICs of AP for P. haemolytica, M. lysodeikticus, and P. aeruginosa varied slightly depending upon the concentration of NaCl and MIC's generally increased slightly with increasing NaCl concentrations. The MIC of lysozyme for P. haemolytica and M. lysodeikticus also increased slightly with increasing NaCl concentrations. The MIC of lysozyme for P. aeruginosa was greater that 50 ug/ml and did not vary with increasing NaCl concentrations. When AP was combined with lysozyme in 50, 100, or 150 mM NaCl conditions, there was a slight antagonistic interaction at high lysozyme and salt concentrations that increased the MIC of AP for all 3 organisms. In conclusion, lysozyme and AP appear not to significantly interact at physiologically relevant concentrations.