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Title: ANTIMICROBIAL AGENTS OF THE MAMMALIAN LUNG

Author
item HUTTNER, KENNETH - CHILDREN'S HOSP,BOSTON,MA
item PIRAINO, JOSEPH - CHILDREN'S HOSP,BOSTON,MA
item Brogden, Kim

Submitted to: American Pediatric Society / The Society for Pediatric Research
Publication Type: Abstract Only
Publication Acceptance Date: 5/1/1998
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: Antimicrobial peptides are abundant components of the innate immune system. These molecular agents may play a key role in neonatal lung immunity based on: (1) the demonstration that their inactivation in airway secretions leads to loss of antimicrobial activity against P. aeruginosa and (2) their absence in the developing human fetus. Within the mammalian lung, two distinct classes of broad-spectrum antimicrobial peptides are present: the cationic, salt-sensitive, cys-rich defensins and the anionic, salt-insensit asp-rich peptides. Contrasting markedly in structure, these two elements of innate immunity may function synergistically in host defense. We have isolated and characterized representatives of both classes from sheep as a model for human lung immunity. Sheep beta-defensin 1 is a 42 amino acid cationic peptide containing the 6 conserved defensin-s ic cysteine residues. Sheep heptapeptides H-DDDDDDD-OH, H-GDDDDDD-OH, and DDDD-OH are anionic, Zn-dependent antimicrobial agents. Immunohistochemical localization demonstrates that both classes are present in airway columnar epithelium. Our studies identify specific interactions between these two host defense elements which may alter the antimicrobial milieu and change the pattern of pulmonary pathogen clearance. These results may help explain the recurrence of lung infections in patients subjected to mechanical bypass of airway defenses (e.g. during intubation) or affected by airway epithelial dysplasia (e.g. bronchopulmonary dysplasia.