Article:Role of Cilia in CF

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HEADLINE: YALE UNIVERSITY

Yale researcher reports new role of cilia in cystic fibrosis

Cystic Fibrosis, a fatal lung disease striking one in 2,500 people, may

be

caused by a failure of the cilia to maintain the level of water

associated with

the mucus in the lungs, causing the natural mucus to thicken and become

infected with bacteria, ultimately leading to death, Yale researchers

are reporting.

        

Cilia are hair-like structures projecting from many of the cells in the

body. They function both to move fluids over cell surfaces and in a

sensory

capacity.

      

In 1988, researchers determined that Cystic Fibrosis was due to defects

in

the gene for the Cystic Fibrosis transmembrane conductance regulator

channel (CFTR). CFTR is a passageway or channel through the cell

membrane that allows chloride ions to pass back and forth across the

cell surface to keep cells in ionic balance.

        

Other researchers later found that the problem of " sticky mucus " in

Cystic

Fibrosis lung disease was probably related to the water layer between

the mucus and the cell surface. This water layer provides the

lubrication that makes it possible for the cilia to beat and thereby

propel the mucus, and any bacteria

contained in it, into the throat and out of the body.

       

Because the chloride ions that pass through the CFTR channel regulate

the

height of this water layer, Cystic Fibrosis patients appear to have

decreased

water on the surface of their airways. This in turn causes the mucus to

thicken,

preventing the cilia from moving the mucus out of the lungs, and results

in a

fertile ground for growth of bacteria which ultimately are fatal.

        

Studies led by Lotte Pedersen and Stefan Geimer, post doctoral research

associates in Professor Rosenbaum's laboratory in the Department of

Molecular, Cellular and Developmental Biology at Yale, now show that the

CFTR

channels are present principally on the cilia that cover the surface of

the

cells in the airways.

        

" The cilia cover the surface of most cells in the airways and poke right

into the water layer, " Pedersen said. " It makes a lot of sense that CFTR

is

present there. "

        

Researchers studying Cystic Fibrosis lung disease initially thought the

problem was with the movement of the cilia, but this turned out not to

be the

case because when the sticky mucus was removed the cilia moved normally.

        

CFTR channels function when the cell senses that the concentration of

salt

or water in the water layer is not normal, and then sends a signal to

CFTR to

let chloride ions flow through to correct the defect. The way the cell

senses

its aqueous environment has so far been a mystery.

        

Rosenbaum said that in other life forms, cilia and flagella are osmotic

sensors and can detect whether the water is too salty or too dilute. If

there

are defects in genes coding for these cilia sensors, the organisms can

no longer

sense their surroundings.

        

" Certain organisms can't back away from a noxious environment, " he said.

" We

propose that the cilia in the airways are also sensory and that they are

involved in regulating the salt and water concentration of the water

layer.

Although the cilia are present in Cystic Fibrosis, they either lack or

have

defective chloride channels that are unable to regulate the water

environment. "

        

Rosenbaum said the finding means that researchers should again look at

the

role of cilia in Cystic Fibrosis, not in terms of the cilia's ability or

failure

to move the mucus out of the lungs, but rather at how the cilia are

sensing the

water environment.

        

" This doesn't tell us how the disease actually occurs, but it points us

in a

new direction, " he said.

        

The findings are being presented today at a meeting of the American

Society

for Cell Biology in San Francisco, Calif.

Becki

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