TV crime drama compound shows immune cells’ misdeeds

Detectives on television shows often spray crime scenes with a compound called luminol to make blood glow. School of Medicine researchers have applied the same compound to much smaller crime scenes: sites where the immune system attacks the body’s own tissues.


The authors reported in Nature Medicine that injected luminol glows blue at sites of active immune inflammation in living mice, and that they can detect this glow from outside the mice with scientific cameras.

Immune inflammation is thought to be a critical component of arthritis and other autoimmune diseases, atherosclerosis, some forms of cancer and neurodegenerative disease. Noninvasively imaging such inflammation should help scientists better understand and control it, the researchers said.

“It’s quite striking how specific and sensitive this approach is,” said senior author David Piwnica-Worms, M.D., Ph.D., professor of radiology and of developmental biology. “For example, we have evidence that this technique can highlight inflamed tissue that is on the way to becoming cancerous but not yet discernible via visual or tactile inspection.”

Piwnica-Worms said cardiologists now say immune inflammation is a key component that makes an arterial plaque dangerous. Such inflammation causes platelets to bind to plaques, leading the plaques to rupture or break away and putting the patient at risk of heart attack, stroke or lung clots.

For now, blood vessels of the chest and torso are too deep within the body to image with this approach. But vessels of the leg and neck are close enough to the skin that the technique may be “directly translatable” to use in human patients, Piwnica-Worms said.

Lead author Shimon Gross, Ph.D., a postdoctoral fellow, proposed that luminol might be used to image inflammation when he found earlier studies linking luminol bioluminescence with myloperoxidase (MPO), a protein some types of immune cells use to make bleach during the inflammatory process. When activated, cells known as phagocytes use MPO to make the bleach in pockets. They seek out and swallow invaders and then push the invaders into the bleach-filled pockets to kill them.

In television dramas like “CSI,” detectives spray a mixture of hydrogen peroxide and luminol onto crime scenes. The mixture reacts with iron from blood, which acts as a catalyst and causes the luminol to glow. In the living body, though, iron isn’t as accessible.

Gross and Piwnica-Worms injected luminol into mice anticipating that they would need a way to distinguish immune inflammation from other processes that might also cause the luminol to luminesce. Instead, they found the compound only glowed at sites of immune inflammation involving MPO. In mice lacking the MPO gene, no glow could be detected.

To further test the new technique, Lee Ratner, M.D., Ph.D., professor of medicine and of molecular microbiology, provided a line of mice that models a type of tumor known to be rife with active immune cells. Injected luminol not only lit up established tumors, but it also highlighted areas of inflammation that would later become tumors.

Scientists also used the technique to show inflammation in a mouse model of acute arthritis. Piwnica-Worms said applying luminol in this context could improve arthritis patient management and enable rapid assessment of the effectiveness of new treatments.