The Glue of Life

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Still, too much inflammation is probably better than none at all. The latter is the peculiar plight of Brooke Blanton, a 13-year-old Dallas girl who has taught researchers much of what they know about cell adhesion and wound healing. Brooke first came to doctors' attention as an infant, when her umbilicus and teething sores failed to close and became infected. Strangely, Brooke's lesions contained no pus -- the carcasses of millions of white cells that pile up at infection sites -- even though her bloodstream was teeming with infection-fighting white cells, or leukocytes.

Mystified, Baylor University physician Donald Anderson and Harvard pathologist Timothy Springer decided to test the child's white cells to see how sticky they were. "There was absolutely no binding at all," says Anderson. A new disease had been discovered: leukocyte-adhesion deficiency. Unable to produce the CAMs that enable leukocytes to stick where they are needed, these rescue cells were sliding past Brooke's wounds like a convoy of ambulances with no brakes. "This child can't heal a paper cut," says Brooke's mother Bonnie. For now, her daughter's life remains a continuous battle against infection, though gene therapists at Baylor hope to cure Brooke by inserting into her white cells a gene for the missing CAM.

Researchers have similar dreams of manipulating stickiness in more commonplace ailments, including cancer. "Cellular-adhesion research isn't going to cure cancer, but it might stop metastasis," says Massachusetts Institute of Technology scientist Richard Hynes. At the La Jolla Cancer Research Foundation in California, genetic scientists have succeeded in inserting a CAM gene inside a tumor cell. Once the cell starts manufacturing patches of biological Velcro, it is essentially "glued in place. It becomes incapable of metastasizing," says Erkki Ruoslahti, president of the foundation. A second approach to controlling cancer is known as "walking on ice." Here the goal is to deny tumor cells traction so they can't grip the walls of blood vessels to implant elsewhere in the body. This may be accomplished by using drugs to block certain CAMs on malignant cells.

While such therapies remain theoretical, reducing stickiness is already proving useful in heart disease, specifically in combatting a dangerous side effect of clot-busting drugs like streptokinase or TPA. Doctors have found that after such drugs are used, lingering pieces of broken-up clots (consisting mainly of platelets) look to surveillance cells like a flood of damaged tissue. Instantly, the inflammation process kicks in: the affected region of the heart becomes sticky and therefore prone to further clotting. Adhesion research has produced a drug now being tested on heart patients that keeps the scattering clot fragments from sticking.