Researchers have pinned down a key protein’s role in keeping the body’s immune system ready to fight infection. The finding, published Oct. 28 in the online edition of the journal Immunity, could point to new ways of treating infections and autoimmune diseases.

Hao Pan, left, and Jack Shively showed CEACAM1 reins in neutrophil development. (Photo by Darrin S. Joy)

John E. Shively, Ph.D., professor and chair of the Department of Immunology, and Hao Pan, graduate student in the Irell & Manella Graduate School of Biological Sciences, found that carcinoembryonic antigen-related cell adhesion molecule 1, commonly called CEACAM1, is crucial to the development of white blood cells called neutrophils.

Neutrophils are the body’s first line of defense against infection by bacteria and other hostile microorganisms. They live for only a few days, so the body must continually produce them. However, if too many neutrophils build up — a condition called neutrophilia — the cells can damage normal tissue.

CEACAM1 helps normal cells grow and develop to form different tissue structures. It also deters tumors from forming and fights the spread of cancer cells. Researchers also know CEACAM1 plays a major role in immune system response and that neutrophils produce relatively large amounts of the protein. Shively and Pan wanted a better idea of what CEACAM1 was doing in neutrophils.

“We know that the protein CEACAM1 is involved in the regulation of white blood cells, but its specific role in neutrophil-dependent host immune responses has not been investigated,” Shively said. “We were interested in determining what would happen to neutrophil-mediated immunity in mice that did not express CEACAM1.”

The researchers found that mice that could not produce any CEACAM1 developed neutrophilia. Digging deeper, they determined that CEACAM1 blocks specific signals that push early white blood cells to become neutrophils.

Further study pointed to another interesting fact: The excess neutrophils provided no protection from bacterial infection. Instead, mice with excess neutrophils succumbed to infection faster than other mice. The scientists believe the excess neutrophils produced high levels of tissue-damaging compounds, which may have increased vulnerability to infection.

Future studies aim to build more understanding of CEACAM1, its role in immune response and how the knowledge might lead to clinical intervention in patients with immune conditions, said Shively.

The National Institutes of Health supported the study.