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Protective proteins - bodyguards at work.

As the immune system patrols the body for biological troublemakers, it regularly strikes out at normal, healthy cells as well. Cells rely on special protective proteins to avoid being the victims of this friendly fire. Two of these tiny bodyguards--called MCP for membrane cofactor protein and DAF for decay accelerating factor--also may help sperm fertilize eggs and protect sperm in the female genital tract, according to researchers at the Washington University School of Medicine. In addition, scientists are looking for ways to recruit MCP and DAF to tell the immune system what to kill and what to leave alone. This research eventually could affect cancer therapy, organ transplantation, and treatments for a wide range of inflammatory diseases.

MCP and DAF sit on the surface of many types of cells and chemically ward off strikes from the immune system. Researchers who found them on the cell membranes of sperm in the late 1980s speculated that sperm carry the proteins for protection in the female reproductive tract, where the immune system is busy fighting bacteria. MCP and DAF belong to an arm of the human immune system called the complement system, or complement, a legion of about 29 proteins, explains John Atkinson, chief of rheumatology. Most members of the complement army spend their time patrolling the bloodstream for invaders. When one is spotted, a complement protein jumps on it and calls on other complement proteins to do the same. The proteins swarm onto the invader and coat it, a signal for a cell-eating member of the immune system to devour it.

MCP and DAF are found on all the tissues that come in contact with the environment, areas where infections try to enter. The placement is logical because this is where the immune system is most active and most likely to injure its own body tissue, Atkinson points out. The common battlegrounds are skin; linings of the digestive and respiratory tracts, blood vessels, and lungs; and blood cells. "I suspect that any time inflammation starts to take place in a tissue where they are not present, MCP and DAF can be formed. Otherwise your tissue would be very susceptible to being damaged by the complement system."

His findings suggest several roles in reproduction. MCP proteins sit in a cluster at the front of the sperm head, underneath an outer membrane, until just before fertilization, when the membrane dissolves. "It's hard to believe that MCP can protect the sperm as it swims up the female genital tract because it is not even exposed. if it were just there for protection it would be on the outside of the sperm. Its location suggests a specialized role that we do not know about."

One possibility is that sperm might need protection from the enzymes that help them penetrate an egg. Those enzymes also might stimulate the female's immune system to attack sperm. "The other idea is that there is some protein that actually binds to MCP and helps the sperm get inside," Atkinson explains.

Unlike MCP, DAF probably does protect sperm during their journey to the egg. DAF sits on the entire sperm head, and even along the tail. It is possible, though not proven, that lack of DAF may account for some male infertility.

Although it may be years away, Atkinson and his colleagues believe the proteins eventually could be used as protection against complement damage in a host of diseases. Complement sees damaged or dying tissue the same way it sees foreign tissue. That damaged tissue and the healthy tissue around it need protection from complement to survive. Heart attacks are one example. "The initial heart damage is caused from blocking a heart artery. But as tissues start to die, they activate complement, and that causes secondary damage," indicates Douglas Lublin, assistant professor of pathology and medicine. Giving MCP and DAF by injection or some other method may provide the needed protection.

The proteins show promise for allowing physicians to fool the immune system into killing cancerous cells. Tumor cells often carry as many as 10 times the normal amount of MCP and DAF, making them extremely difficult for the immune system to destroy, but antibodies available to block the actions of the protective proteins. If these antibodies could be sent to MCP and DAF only on tumor cells, the cancer cells would be helpless victims of the patient's own immune system. "It works very well in a test tube," Atkinson notes. The difficulty is being able to deliver the proteins only to tumor cells.
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Title Annotation:immune system
Publication:USA Today (Magazine)
Date:Feb 1, 1993
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