Science_-_6_March_2020

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SCIENCE sciencemag.org

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S


eeking a new treatment for peo-
ple who have dangerous block-
ages in their coronary arteries,
doctors in London are trying to
disarm the body’s own defend-
ers. The 90 patients in the study
receive the usual treatments for
heart disease, such as small tubes
called stents to prop open their
narrowed arteries. But half of the patients
in the phase II trial, conducted by clinical
pharmacologist Albert Ferro of King’s Col-
lege London and colleagues, also pop pills
targeting a class of immune cells called
neutrophils. Researchers think that by in-
vading the fatty obstructions, or plaques,
in clogged arteries, neutrophils make them
even more dangerous. The drug is designed
to steer the cells away.

Interfering with neutrophils is an auda-
cious idea. Neutrophils make up some 70%
of the white cells in blood, with billions
spawned every day by stem cells nestled in
the bone marrow. The cells patrol the blood-
stream and wage war on pathogens, and
their defensive role is so vital that people
who lose their neutrophils in the course of
cancer treatment can die from infections.
But their scorched-earth tactics are tough
on the body. “They are the classic double-
edged sword,” says immunologist Michael
Fessler of the U.S. National Institute of En-
vironmental Health Sciences. For example,
the enzyme neutrophil elastase, which neu-
trophils release to kill invading bacteria, also
erodes the extracellular matrix, the mesh of
proteins and sugars that cradles cells and
provides structural support for tissue.

Neutrophils can also malfunction. In
some conditions, such as chronic obstruc-
tive pulmonary disease (COPD), they seem
to lose their sense of direction: Instead of
homing in on bacteria, they wander. Re-
searchers suspect these vagrant neutrophils
release neutrophil elastase and other mol-
ecules at the wrong spots, including the
lungs, causing the tissue damage seen in
COPD. And as people age, neutrophils be-
come less effective at combating infections
and more harmful to the body.
“We are now beginning to understand
that neutrophils are linked to many diseases
that blight our population,” says pulmono-
logist Elizabeth Sapey of the University of

Neutrophils fiercely attack infections,


but can also trigger disease. Researchers


are trying to tame them By Mitch Leslie


THE BODY’S


DANGEROUS


DEFENDERS


FEATURES


A neutrophil (orange) traps bacteria by extruding a
net of DNA—a protective response that can backfire.

6 MARCH 2020 • VOL 367 ISSUE 6482 1067
Published by AAAS
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