"Let me tell you about one of the most interesting and underappreciated cells in the immune system," proposes pharmacologist Candace Pert.
With that auspicious introduction, meet the macrophage, a type of white blood cell that neuroscientists like Pert and others believe is probably the key not just to the mind-body interconnection but also to a host of diseases, ranging from arthritis and asthma to lung cancer and even acquired immune deficiency syndrome (AIDS).
Macrophages derive their name from two Greek words meaning large (macro) and eating (phage). Essentially, these white blood cells were long thought to be the clean-up personnel of the immune system. Arising from bone marrow, macrophages are burly and oversized compared with other white blood cells. They're able to devour debris -- including foreign bacteria and dead body cells -- with great ardor.
In recent months, however, reseachers have discovered that macrophages perform far more elegant functions than merely acting as the body's indiscriminate vacuum cleaner. These special white blood cells are essential components of all healing in the body. When the skin is cut, macrophages migrate to the wound, where they not only engage in the cleanup of foreign invaders but also direct other cells called fibroblasts to make repairs.
But that's not all macrophages can do. In a paper set for publication in Science, National Institute of Dental Research immunologist Michael Ruff -- along with coauthors Pert, Sharon Wahl, Larry Wahl and Steven Paul -- report that macrophages can react to drugs formerly believed to act mainly on the brain.
These cells apparently can recognize and react to benzodiazepines, the class of anti-anxiety drugs that includes the well-known Valium and Librium. Other recent evidence suggests that macrophages similarly can identify and react to opiates -- the family of drugs including morphine, heroin and the internally produced beta-endorphins (whose levels rise with physical activity).
Tiny receptors on the macrophages' cell wall allow them to recognize these chemical substances, known as neuropeptides. Receptors operate like a molecule-sized lock. Find the right key -- in this case Valium, or one of the opiates -- and the cell turns on.
The presence of these receptors on macrophages surprised scientists, who once believed that only certain nerve or organ cells such as the pancreas and liver carried these tiny locks specific for neuropeptides. But even more surprising is that "different subsets of macrophages also make neuropeptides," reports Pert -- a finding that suggests "macrophages mediate emotion" and are likely to be a key link between the mind and the body.
Sharon Wahl, chief of the National Institute of Dental Research's section on immunology, has also shown that macrophages play an important role in such diverse diseases as arthritis, tuberculosis and AIDS, although the process is not yet fully understood. In arthritis, Wahl and her group have found that macrophages and other white blood cells are present in the joints. These cells produce a class of substances called lymphokines, which activate other cells, called fibroblasts, to make enzymes that eat away at bone and destroy cartilage. "It's actually like a kind of tumor," Wahl says. What starts the entire process isn't known.
As for AIDS, Wahl has found that the deadly HTLV-III virus also attacks macrophages, not just the white blood cells known as T-cells.
Macrophages also "have a lot to do with cancer," Pert says, "far more than people realized."
Last December, in the journal Science, Pert and NIDR's Ruff demonstrated one intriguing connection between small cell lung cancer cells and macrophages. They found evidence that the so-called small cell cancer cells may not be lung cells at all, but rather renegade macrophages that have begun reproducing out of control. The hypothesis is the subject of a current debate in this week's issue of Science between the Pert and Ruff group and Dr. John Minna's group at the National Cancer Institute.
As for the ultimate mind-body interconnection, there's even evidence, proposed by Ruff and Pert in the August issue of the Journal of Immunology, that macrophages may migrate to the brain. There, this theory suggests, these white blood cells are transformed into the thousands of brain cells known as glial cells. If the idea sounds far-fetched, consider this: macrophages and glial cells share some important characteristics, including the ability to produce potent substance such as interleukin 1, which has profound effects on the central nervous system and the immune system.