Allergy-Associated White Blood Cell Triggers Stem Cell-Mediated Muscle Repair

White blood cells help our bodies ward off invasions from microorganisms, but they serve other purposes too. Once white blood cell in particular, the “eosinophil” helps us when we are infected by multicellular parasites (worms and the like). Eosinophils, however, also play a more unpleasant role, and that is in allergies. When we suffer from allergies, eosinophils multiply and move to our lungs and other places, where they mediate inflammation and tissue damage. Thus eosinophils are the white blood cells we all love to hate.

However, researchers at the University of California, San Francisco (UCSF) have generated new data that, in their view, suggests that eosinophils also play an integral role in muscle regeneration.

Ajay Chawla, Associate Professor at the Cardiovascular Research Institute at UCSF and


lead researcher for this study, said, “Eosinophils are needed for the rapid clearance of necrotic debris, a process that is necessary for timely and complete regeneration of tissues.”

Chawla’s laboratory showed that eosinophils serve double duty when it comes to muscle repair. First, they remove the cellular debris that results from damaged tissues. Secondly, eosinophils secrete a protein called “Interleukin 4” or IL-4. IL-4 triggers a specific type of stem cell to replicate and repair muscle tissue.


According to Chawla, “Without eosinophils you cannot regenerate muscle.”

These eosinophil-activated stem cells are known as “fibro/adipogenic progenitors” (FAP). Until recently, the general thinking surrounding FAPs was that they could only form fat tissue (see Natarajan A., Lemos DR, and Rossi FM, Cell Cycle 2010 9(11): 2045-6).  However, when FAPs are exposed to IL-4, they begin to differentiate into muscle fibers.

“They wake up the cells in muscle that divide and form muscle fibers,” said Chawla

“Bites from venomous animals, many toxicants, and parasitic worms all trigger somewhat similar immune responses that cause injury. We want to know if eosinophils and FAPs are universally employed in these situations as a way to get rid of debris without triggering severe reactions such as anaphylactic shock,” said Chawla.

Allergy-Relevant Stem Cell Affected by Smoking

A research team at the Helmholtz Center for Environmental Research (UFZ) led by Drs. Irina Lehmann and Kristin Weiβe has found evidence for a link between a particular stem cell population and environmental toxins.  These results could have significant implications for allergy sufferers.

All the blood cells are made by hematopoietic stem cells in the bone marrow.  These bone marrow stem cells divide to renew themselves and generate progenitor cells that can divide a little and differentiate into specific types of blood cells.  The progenitor cells spend some time in the bone marrow, but are released into the peripheral bloodstream to replenish lost blood cells.

One particular progenitor cell is called the eosinophil/basophil progenitor, and this multipotent stem cells can either differentiate into an eosinophil or a basophil.  Eosinophils help fight parasite infections, but they also play an important role in allergies.  Basophils can fight infections, but they also become stationary in tissue and are known as mast cells where they can release chemicals that cause allergies in response to allergen, which are substances that cause allergies.

Several previous studies have shown that allergy sufferers, be they children or adults, have higher levels of eosinophil/basophil progenitor cells circulating in their blood, and that those individuals whose umbilical blood has higher levels of circulating eosinophil/basophil progenitor cells are at higher risk for allergies later in life.

The UFZ team wanted to clarify the relationship between allergies and the presence of eosinophil/basophil progenitor cells.  Since environmental toxins are known to stimulate allergies in younger people, they hypothesized that environmental toxins might increase the quantity of circulating eosinophil/basophil progenitor cells in young children.

Lehmann and Weiβe examined blood samples from 60 one-year old children and used skin tests to measure the tendency of these children to form rashes after exposure to allergens (substances that cause allergies).  The skin tests are a measure of the sensitivity of the children to allergies.  They also measured the levels of environmental toxins  to which the children’s families were exposed.

The results from this study were remarkable.  Children whose families were exposed to higher levels of volatile organic compounds or VOCs, which are quite prevalent in cigarette smoke, showed higher levels of circulating eosinophil/basophil progenitor cells and were more sensitive to allergens.  Thus the environmental influences seemed to influence the levels of those stem cells known to sensitize people to allergies.

Lehmann noted:  “That VOCs, large amounts of which are released with cigarette smoke, have the greatest effect on stem cells was not entirely unexpected.”

Adding to this, Weiβe said:  “Just as important, however, is that we can show that alterations in the number of stem cells as a result of harmful substances that place only in children who have been afflicted with skin manifestations.”  Thus there is a direct relationship between someone’s genetic predisposition for a disease and the environmental influences to which they are exposed.  Another way to say this would be that there are environmental and lifestyle factors which determine whether a genetic predisposition to have allergies results in actually suffering from allergies.  The environmental effects influence the levels of a circulating stem cell known to play a role in allergies.