Australian researchers have identified a new protein in human airway epithelial cells that regulates allergic airway inflammation. This protein—adipocyte/macrophage fatty acid–binding protein (aP2)—is known to regulate the uptake of fatty acids by fat cells and has been previously linked to insulin resistance in diabetes and the development of atherosclerosis. This new study suggests that in addition to its role in type-2 diabetes and hardening of the arteries, aP2 plays an essential role in allergic airway diseases, such as asthma, and offers an additional intriguing link between the immune and metabolic systems. The study appeared online on July 13 in advance of print publication in the August issue of the Journal of Clinical Investigation.
The “hygiene hypothesis” of the underlying causes of asthma currently dominates thinking in the medical field. The hypothesis proposes that childhood infection and environmental factors such as diet and airborne pollution contribute to a predisposition to this condition. Michael Rolph and colleagues from The Garvan Institute of Medical Research, Sydney, now show for the first time that the protein aP2 is present in human epithelial cells lining the tubes that carry air from the windpipe to the lungs (bronchi), and that aP2 expression is significantly increased when these cells are stimulated with the molecules interleukin-4 and –13. This finding was very unexpected as aP2 has previously been considered to be a specific marker for fat cells. The Garvon group went on to show that mice lacking aP2 have a dramatic reduction in airway inflammation in a model of asthma. In addition, the infiltration into the airways of inflammatory molecules such as leukocytes and eosinophils was highly dependent on aP2 function in mice. The data emphasize the importance of lipids in the inflammatory response and contribute to the emerging theme that an overlap exists between the pathways that regulate inflammation and those that govern metabolism. Finally, the study suggests that blocking aP2 function may be a novel approach for the treatment of asthma and other inflammatory lung diseases.