Special Delivery to the Lymph Node

Science Signaling  03 Nov 2009:
Vol. 2, Issue 95, pp. ec352
DOI: 10.1126/scisignal.295ec352

The adaptive immune response to infection depends on the enhanced recruitment of lymphocytes to draining lymph nodes (DLN) and their retention therein, enhancing the likelihood that the appropriate lymphocytes will encounter antigen-presenting cells from the affected peripheral tissues. DLN undergo rapid growth and vascular remodeling to accommodate this process, but how the peripheral signals that stimulate them to do so reach the DLN has been unclear. Kunder et al. investigated the possibility that the insoluble granular particles released from mast cells (MC) during degranulation might act as chaperones that protect signaling molecules, such as tumor necrosis factor (TNF), on the journey from the periphery to the DLN. Scanning electron micrographs of isolated rat peritoneal mast cells revealed that exposure to a small molecule MC activator (compound 48/80) led to the gradual release of stable spherical particles. Immunoblot analysis of purified particles indicated that TNF was present in these particles; moreover, a green fluorescent protein (GFP)–TNF fusion protein localized to particles derived from a rat MC line or mouse bone marrow–derived MCs. Visualization of rat mesentery and mouse footpad lymphatics indicated that MC-derived particles trafficked within the lymphatic system, and particles from MCs activated in footpad were detected in DLN. MC-derived particles from wild-type mice stimulated lymph node hypertrophy when injected into the footpads of MC-deficient mice, whereas particles from mice lacking TNF did not. MC-derived particles are composed primarily of heparin proteoglycans and positively charged proteases, and TNF encapsulated in synthetic heparin-chitosan particles was more effective than soluble TNF at eliciting lymph node enlargement. The authors thus conclude that MC-derived particles provide a mechanism for the safe delivery of signaling factors from inflamed tissues to the DLN.

C. A. Kunder, A. L. St. John, G. Li, K. W. Leong, B. Berwin, H. F. Staats, S. N. Abraham, Mast cell–derived particles deliver peripheral signals to remote lymph nodes. J. Exp. Med. 206, 2455–2467 (2009). [Abstract] [Full Text]