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Mast cells know how to maintain long-distance relationships. Rather than sending diluted, mixed signals, they dispatch concentrated messages to distant contacts bound in tightly wrapped packages, according to Kunder et al.
Many cells secrete soluble molecules that help maintain the body's physiology. For example, β cells in the pancreas release large quantities of insulin into the circulation to control blood glucose levels. Here, Kunder and colleagues discover an alternative form of signal transport that comes in handy when signaling molecules are short lived or produced in small quantities.
This group previously found that TNF secreted by tissue mast cells reached draining lymph nodes quickly and was required for the nodes to expand in response to infection. But no one knew how this short-lived cytokine traveled from the periphery to remote lymph nodes without being diluted or degraded along the way.
The new study reveals that mast cells activated in the foot pads of mice released insoluble heparin-based particles that contained TNF. The particles entered lymphatic vessels, presumably through gaps in lymphatic endothelial cells, and drained into regional lymph nodes. After the particles entered, the lymph nodes doubled in size, indicating that TNF had been released. Soluble TNF injections had little effect on lymph nodes. Likewise, without TNF, the particles had no effect.
The particles protect TNF from dilution and degradation as it travels to the lymph node, suggests senior author Soman Abraham. “If Aspirin wasn't enteric coated,” he explains, “you'd have to take an awful lot of it for it to work.” How the particles release their contents once in the lymph node remains unknown.