title: Elafin (elastase-specific inhibitor) has anti-microbial activity against gram-positive and gram-negative respiratory pathogens.
abstract: Elafin (elastase-specific inhibitor) is a low molecular weight inhibitor of neutrophil elastase which is secreted in the lung. Using synthetic peptides corresponding to full-length elafin (H2N-1AVT.....95Q-OH), the NH2-terminal domain (H2N-1AVT.....50K-OH) and the COOH-terminal domain (H2N-51PGS.....95Q-OH), we demonstrate that elafin's anti-elastase activity resides exclusively in the COOH-terminus. Several characteristics of elafin suggest potential anti-microbial activity. The anti-microbial activity of elafin, and of its two structural domains, was tested against the respiratory pathogens Pseudomonas aeruginosa and Staphylococcus aureus. Elafin killed both bacteria efficiently, with 93% killing of P. aeruginosa by 2.5 microM elafin and 48% killing of S. aureus by 25 microM elafin. For both organisms, full-length elafin was required to optimise bacterial killing. These findings represent the first demonstration of co-existent anti-proteolytic and anti-microbial functions for elafin.
authors.affiliation: Rayne Laboratory, University of Edinburgh Medical School, UK.
authors.forename: A J
authors.initials: AJ
authors.lastname: Simpson
authors.forename: A I
authors.initials: AI
authors.lastname: Maxwell
authors.forename: J R
authors.initials: JR
authors.lastname: Govan
authors.forename: C
authors.initials: C
authors.lastname: Haslett
authors.forename: J M
authors.initials: JM
authors.lastname: Sallenave
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000302:isolation & purification; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors; D010446:Peptide Fragments / Q000494:pharmacology; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000494:pharmacology*; D011552:Pseudomonas Infections / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000302:isolation & purification; D012141:Respiratory Tract Infections / Q000382:microbiology*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification
chemical_list: D000935:Antifungal Agents; D010446:Peptide Fragments; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D015842:Serine Proteinase Inhibitors; D010196:Pancreatic Elastase