Submitted to: Proceedings of the National Academy of Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: September 18, 1995
Publication Date: N/A
Interpretive Summary: The lungs are constantly in contact with microorganisms inhaled with dusts and aerosols from the external environment. In spite of this, the lungs remain relatively disease-free due to a number of nonspecific immune mechanisms that rid of inhaled organisms before they can persist and cause disease. One mechanism may be due to small proteins recently found in lung gfluid that act as natural antibiotics. In this study, we isolated small protein antibiotics from lung fluid that can kill the bacterium that causes shipping fever of cattle. The proteins were analyzed (to determine their composition and structure) and chemically made in larger amounts for laboratory studies. The proteins are small, relative resistant, and may represent a new class of natural antibiotics. These antibiotics may be given to prevent disease or given to treat pneumonia.
Ovine pulmonary surfactant is bactericidal for Pasteurella haemolytica after surfactant and bacteria mixtures are incubated with normal ovine serum. Previous work implicated a small, proteinaceous component. To isolate this component, surfactant was separated by high performance liquid chromatography (HPLC). Three fractions (fraction 2, fraction 3, and fraction 6) induced killing of P. haemolytica by normal ovine serum. By amino acid and sequence analysis, fraction 2 contained heptapeptide with an N-terminus of glycine followed by 6 repeating Asp; fraction 3 contained a homopolymer of 7 Asp; and fraction 6 contained a peptide with an N-terminus of glycine and Ala followed by 5 repeating Asp (fraction 6). Synthesized peptides, called surfactant-associated anionic peptide (SAAP), in zinc saline solution induced killing similar to surfactant by normal serum but peptides in phosphate buffer, pH 7.2 did not. Extracellular in pulmonary secretions, these peptides may help clear certain gram-negative bacteria from the lungs of sheep as a part of the pulmonary innate defense system.