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Title: DIFFERENCES IN THE CONCENTRATION OF SMALL, ANIONIC ANTIMICROBIAL PEPTIDES IN BRONCHOALVEOLAR LAVAGE FLUID AND THEIR PRESENCE IN RESPIRATORY EPITHELIUM OF PATIENTS WITH AND WITHOUT CYSTIC FIBROSIS.

Author
item Brogden, Kim
item ACKERMANN, MARK
item MCCRAY, PAUL
item HUTTNER, KENNETH

Submitted to: Infection and Immunity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/17/1995
Publication Date: N/A
Citation: N/A

Interpretive Summary: Respiratory tract diseases are a leading cause of loss from disease in the cattle, sheep and goat industries. Annual loss in the United States is estimated to exceed one billion dollars. Losses are from mortality, reduced feed efficiency, and slaughter condemnations, as well as prevention and treatment measures. Currently, not all the factors leading to the development of pneumonia are known by scientists and veterinarians. As part of our ongoing studies to understand the disease process, we found that the respiratory tract contains a number of natural antibiotics. In this study, we were able to show that these natural antibiotics are conserved being found in respiratory tract secretions and upper respiratory tract lining cells and antibodies made against sheep antimicrobial peptides react with similar peptides in humans. This provides the background for prospective studies of the role of these natural antibiotics in the etiology and treatment of many respiratory infections. Our findings are a important first step in the development of a new treatment that can be used to better control shipping fever of cattle. Corollary benefits include an increase in the profitability and international competitiveness of the U. S. cattle industry, a stronger rural economy, and a continued supply of inexpensive, wholesome beef, and beef products for the American consumer.

Technical Abstract: Affinity-purified rabbit polyclonal (PAB96-1) and mouse monoclonal (1G9- 1C2)antibodies were prepared to synthetic H-DDDDDDD-OH, an antimicrobial anionic peptide (AP) originally isolated from ovine pulmonary surfactant. Both antibodies were used to assess the concentration of AP-like molecules in native human bronchoalveolar lavage fluids (47 patients) and pulmonary tissues (6 patients). ELISA concentrations of AP-like molecules were significantly lower in 13 patients with CF (0.78 mM + 0.46 mM SD; P = 0/01) than in 34 patients without CF (1.30 mM + 0.66 mM SD). Immunohisto- chemistry staining of pulmonary tissues also differed. In patients without CF, very little antigen was stained in the apical cytoplasm of the bronchial and bronchiolar epithelium yet robust staining was seen in the alveolar epithelium. In patients with CF, robust staining of antigen was seen in the apical cytoplasm of the bronchial and bronchiolar epithelium yet no staining was seen in the alveolar epithelium suggesting that patients with CF have decreased levels of AP-like molecules.