THE PEPTIDE ANTIBIOTIC LL-37 HCAP-18 IS EXPRESSED IN EPITHELIA OF THEHUMAN LUNG WHERE IT HAS BROAD ANTIMICROBIAL ACTIVITY AT THE AIRWAY SURFACE/

The airway surface is an important host defense against pulmonary infe ction. Secretion of proteins with antimicrobial activity from epitheli al cells onto the airway surface represents an important component of this innate immune system. Defensins are the best characterized epithe lial-derived peptide antibiotics. A member of another family of peptid e antibiotics called cathelicidins recently was identified from human bone marrow. We show in this paper that this human peptide named LL-37 /hCAP-18 also may play a role in innate immunity of the human lung. In situ hybridization localized high levels of LL-37/hCAP-18 RNA to surf ace epithelial cells of the conducting airway as well as serous and mu cous cells of the submucosal glands. LL-37/hCAP-18 peptide with antimi crobial activity was partially purified from airway surface fluid from human lung and a human bronchial xenograft model, The synthetic pepti de LL-37 demonstrated antibiotic activity against a number of Gram-neg ative and Gram-positive organisms including Pseudomonas aeruginosa; ba cterial killing of LL-37 was sensitive to NaCl and was synergistic wit h lactoferrin and lysozyme. In summary, we show that LL-37/hCAP-18 is a peptide with broad antimicrobial activity that is secreted onto the airway surface from epithelial cells of the human lung.