In a surprise finding, scientists have discovered that histamine, the inflammatory compound released during allergic reactions that causes runny nose, watery eyes and wheezing, can be produced in large amounts in the lung by neutrophils, the white blood cells that are the major component of pus.
Pus, a fluid found in infected tissue, is produced as a result of inflammation.
The study in mice is the first to show that lung neutrophils can produce histamine in significant quantities, according to principal investigator George Caughey, MD, chief of pulmonary/critical care medicine at the San Francisco VA Medical Center.
“Previously it was thought that the primary sources of lung histamine, in health as well as disease, was mast cells, which are classically associated with allergy,” notes Caughey, who is also a professor of medicine at the University of California, San Francisco.
Caughey says the result could mean that histamine acts as a link between airway infections and asthma and bronchitis, which are associated with allergy. “In both, we observe inflammation ?? swelling, blood vessel leak, and muscle contraction that narrows the airway.” The study appears in the January 2007 issue of the Journal of Experimental Medicine.
Caughey was investigating the well-known fact that upper respiratory infections often trigger acute asthma attacks. “We hypothesized that an infection in the airway would release histamine from mast cells, and that would be one of the reasons,” he explains.
To test the hypothesis, Caughey and his team exposed two different populations of mice to mycoplasma, a common respiratory infection in rodents and humans. One population had a genetic abnormality that causes a total lack of mast cells; the other population was made up of normal, wild-type mice. Both populations of infected mice developed pneumonia.
“We thought the mice without mast cells would do better than the wild-type mice, because the infection wouldn’t be provoking mast cells to release histamine,” recalls Caughey. “In fact, they did much worse. Even though there were no mast cells, histamine levels rose up to 50 times normal.” The reason was straightforward, Caughey says. Neutrophil numbers increased in response to infection, and neutrophils in turn produced histamine. “It’s a direct effect of the mycoplasma bacteria on neutrophils. They induce neutrophils to produce the enzyme that produces histamine.”