June 16, 1997
Media Contact: Michael Purdy
Hopkins scientists studying lung damage from cystic fibrosis (CF) have found a natural "bug spray" that lung cells "squirt" on attacking bacteria.
The "spray", an antimicrobial compound researchers call hTAP(human tracheal antimicrobial peptide), appears to be disabled in CF patients, increasing their vulnerability to lung infections. If researchers can mass-produce hTAP or similar compounds, they may help fight lung infections in both CF patients and in the general population, where infectious lung diseases like tuberculosis kill more than 7 million people every year.
"People have always thought that the lungs only attacked infections via the classical immune system--B cells, T cells and other immune cells," says Pete Pedersen, Ph.D., Hopkins professor of biological chemistry. "But lung cells apparently have their own first-line defense mechanism--they shoot out one or more peptides that kill bacteria."
After the first such compounds were identified in cells from frog skin and cow throats by researchers at other institutions Young Hee Ko, a research associate in Pedersen's lab, suspected that CF jammed the "nozzle" on a similar bug spray.
"That nozzle is a channel on the surface of lung cells called CFTR, and we already knew that CF disrupts it," says Ko.
In a study funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the Cystic Fibrosis Foundation, Ko exposed two batches of lung cells, one from a normal patient and one from a CF patient, to Pseudomonas aeruginosa, a bacterium that causes repeated lung infections in CF patients.
The bacteria infected many CF cells while making little progress in the normal cells. Ko then searched for an antimicrobial compound similar to the one found in cow throats, and found hTAP.
Pedersen speculates that cells in other areas at high risk for infection, such as the eyes, the gut or the mouth, may secrete similar germ-fighting compounds.
Their results were published recently in the journal FEBS (Federation of European Biochemical Societies) Letters. The other study author was Michael Delannoy, an electron microscopist.