The not-so-dispensable spleen

It’s high time somebody said something nice about the lowly spleen. The much-maligned organ serves as a holding tank for ready-to-go immune agents called monocytes, a new study finds. These simple cells are first responders to trouble sites in the body, and the spleen is their main dispatcher, researchers report in the July 31 Science.

While it’s true that people can survive without a spleen, the organ is far from worthless. It recycles iron from old red blood cells, houses fresh blood cells, synthesizes antibodies and acts as a chamber in which pathogens are killed.

In the new study, scientists add to this list of duties, showing that the spleen stores monocytes in compartments close to mainstream blood vessels. This allows monocytes to travel to trauma and infection sites on short notice, says study coauthor Mikael Pittet, an immunologist at HarvardMedicalSchool in Boston. “Timing is a really important issue when you want to fight pathogens or heal after an injury,” he says.

Monocytes are formed in the bone marrow and circulate in the blood stream. When the immune system detects an infection or trauma, immune proteins usher monocytes to trouble sites. There, a first wave of inflammatory monocytes engulfs pathogens, takes apart dead cells and cleans up debris from the battle. After a few days, a second wave, this time of anti-inflammatory monocytes, arrives to foster the rebuilding process.

Pittet teamed with Harvard colleagues Filip Swirski, Matthias Nahrendorf and others to ascertain these monocytes’ origins.

In a series of experiments in which they induced heart attacks in mice, the researchers showed that many monocytes arriving at traumatized heart tissue could be traced back to the spleen.

Further tests showed that the compound angiotensin-II, which is released into the blood during cardiac trauma, is needed to draw monocytes out of the spleen. Mice engineered to lack an angiotensin-II receptor failed to recruit monocytes from the organ, hindering healing in the heart. Other messenger proteins may also recruit monocytes, Pittet says.

The new findings may also shed light on the downside of monocytes. Too many monocytes from the first wave can rev up inflammation too much. Since inflammation plays a deleterious role in cancer and many autoimmune diseases, a better understanding of monocytes’ migration from the spleen might offer ways to combat these diseases, Pittet says.

The additional duties of the spleen may raise further doubts about whether its removal is a good idea. In 1977, scientists reported that servicemen who had undergone spleen removal during World War II had higher rates of death due to diseases in general — and from heart disease and pneumonia specifically — during the 28 years following the war, compared with similar men who kept their spleens.

Spleen removal can indeed cause diminished response to some vaccines and increased susceptibility to infections, note Ting Jia and Eric Pamer of Memorial Sloan Kettering Institute in New York City, writing in the same issue of Science. With the new finding, they argue, “the organ gains some new respect.”