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Shedding New Light on Lupus

Posted on: Friday, 5 September 2003, 06:00 CDT

Study finding offers new information about inflammation in disease

HealthDayNews -- American scientists have gained new insight about how the body eliminates dead cells, information that could lead to new ways for treating lupus or cancer, or for preventing infections following trauma.

Researchers at Duke University Medical Center and the Durham VA Hospital found the specialized cells called macrophages that clear dead cells have a much more complicated and important function than previously understood.

Their study appears in the Sept. 15 issue of Blood.

When macrophages fail to remove dead cells, the contents of the dead cells (including DNA) can trigger an immune system response, which can weaken a person's body and leave him susceptible to infection after a trauma injury.

In people with lupus, the contents of these dead cells may form immune complexes with antibodies. This can result in painful inflammation that may damage such organs as the kidneys.

It's long been believed that DNA from dead cells is present in the bloodstream only when macrophages become overwhelmed with more dead cells than they can handle. But this new study says that may not be the case.

In one experiment, the scientists injected a large quantity of dead cells into normal mice, which increased the amount of DNA in the animals' blood. In a second experiment, the scientists created mice that lacked macrophages. These mice were also injected with a large quantity of dead cells.

Because these genetically engineered mice lacked macrophages, the scientists expected to find all of the dead cell DNA in the mice's bloodstreams. But they found no DNA from the dead cells.

"This result was totally unexpected, and caused us to step back and consider how the macrophages function to remove cell waste," researcher Dr. David Pisetsky, chief of Duke's division of rheumatology and immunology, says in a news release.

He and his colleagues theorize that, without macrophages, dead cells can't be broken down efficiently enough for DNA to appear in the bloodstream at a detectable level. Cells that aren't processed by macrophages and eliminated from the body may accumulate and cause inflammation.

"What we hypothesize is that uptake by macrophages is not just part of the process, but is absolutely crucial to the appearance of DNA from dead cells in the blood. The macrophages can't be bypassed by the dead cells, even if there is more cell DNA than they can process," Pisetsky says.

If this theory is correct, it means macrophages have a much more important function than previously recognized. That could have major implications for the treatment of lupus and other inflammatory conditions.

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On the Net:

Lupus information

Duke University Medical Center

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