Cholesteryl Linoleate Supplementation Increases the Inherent Antibacterial Activity of Bronchioalveolar Lavage Fluid against Pseudomonas aeruginosa

Innate immunity is the first line of host defense against invading microorganisms. Host-derived lipids including cholesteryl linoleate (CL) contribute to the antibacterial defense in the airways. Cystic fibrosis (CF) is a genetic disorder that leads to thick mucus production and chronic lung infections with opportunistic pathogens, frequently Pseudomonas aeruginosa, causing premature death. Our collaborators have developed a pig animal model of CF. Preliminary studies from our laboratory employing bronchioalveolar lavage fluid from pediatric CF patients and non-CF disease controls suggested that in CF cholesteryl linoleate levels are reduced. This was accompanied by a diminished antibacterial activity. To assess whether external addition of CL can augment the inherent antibacterial activity of BALF we subjected BALF from wild type pigs with and without supplementation with CL at physiological concentrations (40 mg/mL) to colony forming unit assays with P. aeruginosa. We found an increase of the antibacterial activity after addition of CL suggesting that the administration of CL in the airways as inhalant might improve the clinical course of CF. Considering that the airway secretions in CF are very mucoid mitigating the use of CFU assays, we have begun to develop a fluorescent based assay to measure bacterial proliferation and antimicrobial effects of lipids including CL formulated in liposomes. This will allow us to test the feasibility of external addition of CL in CF patients. Our research may lead to improved therapy and prophylaxis of chronic lung infection in CF.