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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