title: Lipids including cholesteryl linoleate and cholesteryl arachidonate contribute to the inherent antibacterial activity of human nasal fluid.
abstract: Mucosal surfaces provide first-line defense against microbial invasion through their complex secretions. The antimicrobial activities of proteins in these secretions have been well delineated, but the contributions of lipids to mucosal defense have not been defined. We found that normal human nasal fluid contains all major lipid classes (in micrograms per milliliter), as well as lipoproteins and apolipoprotein A-I. The predominant less polar lipids were myristic, palmitic, palmitoleic, stearic, oleic, and linoleic acid, cholesterol, and cholesteryl palmitate, cholesteryl linoleate, and cholesteryl arachidonate. Normal human bronchioepithelial cell secretions exhibited a similar lipid composition. Removal of less-polar lipids significantly decreased the inherent antibacterial activity of nasal fluid against Pseudomonas aeruginosa, which was in part restored after replenishing the lipids. Furthermore, lipids extracted from nasal fluid exerted direct antibacterial activity in synergism with the antimicrobial human neutrophil peptide HNP-2 and liposomal formulations of cholesteryl linoleate and cholesteryl arachidonate were active against P. aeruginosa at physiological concentrations as found in nasal fluid and exerted inhibitory activity against other Gram-negative and Gram-positive bacteria. These data suggest that host-derived lipids contribute to mucosal defense. The emerging concept of host-derived antimicrobial lipids unveils novel roads to a better understanding of the immunology of infectious diseases.
authors.affiliation: Department of Biological Sciences, California State University, Los Angeles, CA 90032, USA.
authors.forename: Thai Q
authors.initials: TQ
authors.lastname: Do
authors.forename: Safiehkhatoon
authors.initials: S
authors.lastname: Moshkani
authors.forename: Patricia
authors.initials: P
authors.lastname: Castillo
authors.forename: Suda
authors.initials: S
authors.lastname: Anunta
authors.forename: Adelina
authors.initials: A
authors.lastname: Pogosyan
authors.forename: Annie
authors.initials: A
authors.lastname: Cheung
authors.forename: Beth
authors.initials: B
authors.lastname: Marbois
authors.forename: Kym F
authors.initials: KF
authors.lastname: Faull
authors.forename: William
authors.initials: W
authors.lastname: Ernst
authors.forename: Su Ming
authors.initials: SM
authors.lastname: Chiang
authors.forename: Gary
authors.initials: G
authors.lastname: Fujii
authors.forename: Catherine F
authors.initials: CF
authors.lastname: Clarke
authors.forename: Krishna
authors.initials: K
authors.lastname: Foster
authors.forename: Edith
authors.initials: E
authors.lastname: Porter