BACKGROUND: CAP18 derived from rabbit leukocytes is a 142-amino acid protein recently demonstrated to have Lipopolysaccharide (LPS) binding and anti-microbial activity. The C-terminal 37 amino acids of rabbit CAP18 (CAP18(106-142) comprise the LPS-binding and anti-microbial domain. The homologous domain of human CAP18 (huCAP18(104-140) was identified from the recently cloned human CAP18 cDNA. OBJECTIVES: To evaluate the antimicrobial activity of C-terminal peptides derived from human CAP18. STUDY DESIGN: Prepare synthetic human CAP18(104-140) and study anti-microbial activity versus various gram-negative and gram-positive bacteria. RESULTS: Synthetic human CAP18(104-140) has broad anti-microbial activity versus both gram-positive (IC50 = 2.5 micrograms/ml) and gram-negative bacteria (IC50 = 0.5-5 micrograms/ml). Susceptible strains include Staphylococcus aureus, Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa and Salmonella typhimurium. A 32-amino acid peptide lacking five amino acids from the C-terminus of CAP18(104-140) has higher activity. Unlike previously characterized anti-microbial peptides derived from granulocyte proteins, CAP18(104-140) is active in serum. CONCLUSIONS: Human CAP18(104-140) or a derivative peptide may have therapeutic potential for bacterial sepsis.
BACKGROUND:CAP18 derived from rabbit leukocytes is a 142-amino acid protein recently demonstrated to have Lipopolysaccharide (LPS) binding and anti-microbial activity. The C-terminal 37 amino acids of rabbitCAP18 (CAP18(106-142) comprise the LPS-binding and anti-microbial domain. The homologous domain of humanCAP18 (huCAP18(104-140) was identified from the recently cloned humanCAP18 cDNA. OBJECTIVES: To evaluate the antimicrobial activity of C-terminal peptides derived from humanCAP18. STUDY DESIGN: Prepare synthetic humanCAP18(104-140) and study anti-microbial activity versus various gram-negative and gram-positive bacteria. RESULTS: Synthetic humanCAP18(104-140) has broad anti-microbial activity versus both gram-positive (IC50 = 2.5 micrograms/ml) and gram-negative bacteria (IC50 = 0.5-5 micrograms/ml). Susceptible strains include Staphylococcus aureus, Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa and Salmonella typhimurium. A 32-amino acid peptide lacking five amino acids from the C-terminus of CAP18(104-140) has higher activity. Unlike previously characterized anti-microbial peptides derived from granulocyte proteins, CAP18(104-140) is active in serum. CONCLUSIONS:HumanCAP18(104-140) or a derivative peptide may have therapeutic potential for bacterial sepsis.
Authors: Seth B Coffelt; Frank C Marini; Keri Watson; Kevin J Zwezdaryk; Jennifer L Dembinski; Heather L LaMarca; Suzanne L Tomchuck; Kerstin Honer zu Bentrup; Elizabeth S Danka; Sarah L Henkle; Aline B Scandurro Journal: Proc Natl Acad Sci U S A Date: 2009-02-20 Impact factor: 11.205
Authors: David J Lynn; Rowan Higgs; Susan Gaines; Joanna Tierney; Tharappel James; Andrew T Lloyd; Mario A Fares; Grace Mulcahy; Cliona O'Farrelly Journal: Immunogenetics Date: 2004-05-18 Impact factor: 2.846
Authors: Alvin B Coda; Tissa Hata; Jeremiah Miller; David Audish; Paul Kotol; Aimee Two; Faiza Shafiq; Kenshi Yamasaki; Julie C Harper; James Q Del Rosso; Richard L Gallo Journal: J Am Acad Dermatol Date: 2013-07-18 Impact factor: 11.527