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* Department of Biological Sciences and
Department of Chemistry and Biochemistry, California State University, Los Angeles, CA 90032;
Department of Chemistry and Biochemistry,
The Pasarow Mass Spectrometry Laboratory, The NPI/Semel Institute for Neuroscience and Human Behavior and Department of Psychiatry & Biobehavioral Sciences, University of California, Los Angeles, CA 90095; and
¶ Molecular Express, Rancho Dominguez, CA 90220
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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Grant AI55675 from the National Institute of Allergy and Infectious Diseases, Grant 1P20 MD001824 from the National Institutes of Health, Louis Stokes Alliances for Minority Participation program and its Bridge to the Doctorate Grant HRD-0331537 from the National Science Foundation, Minority Biomedical Research Support Research Initiative for Scientific Enhancement Grant R25 GM61331 from National Institutes of Health, and California State University, Los Angeles and California State University Program for Education and Research in Biotechnology (CSUPERB) grants. Parts of this work have been presented at the 18th Annual CSUPERB Symposium in San Jose, CA, January 17, 2006 and at the 106th General American Society for Microbiology Meeting in Orlando, FL, May 23, 2006.
2 T.Q.D. and S.M. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Edith Porter, Department of Biological Sciences, California State University, 5151 State University Drive, Los Angeles, CA 90032. E-mail address: eporter{at}calstatela.edu
4 Abbreviations used in this paper: HDL, high-density lipoprotein; HNP, human neutrophil peptide; SPE, solid phase extraction; rpHPLC, reversed phase HPLC; ELSD, evaporative light scattering detection; GC/MS, gas chromatography/mass spectrometry; AU, acid urea; apoA-I, apolipoprotein A-I.
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