Mast Cells Linked to Multiple Sclerosis - Brief Article

Applied Genetics News, March, 2000

Scientists at Emory University School of Medicine have uncovered a connection between mast cells and the development of multiple sclerosis (MS), an auto- immune disease that attacks the central nervous system. Extensive research has already led to the development of drugs that effectively block the action of mast cells in other diseases; therefore, the present discovery may lead to the design of effective MS drugs. Until now, research into the mechanisms of multiple sclerosis has been focused primarily on T-cells.

The Emory discovery was reported in the March 5 issue of the Journal of Experimental Medicine. Emory University pathologists Melissa A. Brown and Ginny Secor, a doctoral student, pieced together several parts of a research puzzle to develop their hypothesis that mast cells are linked to MS.

In MS, genetic and/or environmental factors are thought to cause the immune system to mistakenly attack the protective myelin sheath that insulates nerve cells. This results in plaques that impair communication throughout the central nervous system. Although not fatal, multiple sclerosis causes progressively debilitating symptoms in many of its victims, decreasing life expectancy by an average of six years. Problems include weakness, numbness, infections and difficulty performing mental tasks. Symptoms usually begin between 15 and 40 years of age.

Many of the cytokines implicated in MS are produced by mast cells. Although not widely appreciated, previous research had shown that mast cells are prevalent in the central nervous system. Mast cells are also major producers of proteases, shown in the laboratory to have profound effects on degrading the myelin sheath that lines nerves.

Believing that mast cells might play a key role in MS development, Brown and Secor tested their hypothesis using a type of mutant mouse that is deficient in mast cells. They injected myelin proteins designed to induce the mouse counterpart of multiple sclerosis, called experimental allergic encephalomyelitis (EAE). The mast cell-deficient mice exhibited significantly reduced disease incidence, delayed disease onset, and decreased mean clinical scores as compared to normal control animals. After reconstituting the deficient mice with mast cells, disease susceptibility and severity were restored to the levels observed in the normal mice.

In addition to direct release of myelin-damaging proteases, release of vasodilation-inducing histamine by mast cells may facilitate the entrance of T- cells through the blood-brain barrier.

A big question remains, says Brown, as to whether drugs such as antihistamines already used to treat respiratory tract diseases such as allergy and asthma would be effective in treating multiple sclerosis, or whether the drugs would need to be modified in order to gain entry into the central nervous system.