SUMMARY | FULL STORY
IMMUNOLOGY
Remote-control Immunity Up Close
Mechanism Shown for Recruitment of Monocytes to Inflamed Lymph Nodes at Distance from Wound
HMS researchers have discovered a "remote control" mechanism that cells at a wound may use to alert the nearest lymph node and initiate an immune response. Wounds send out chemokines, chemical SOS signals that trigger inflammation and attract leukocytes to the site of infection. Now, a team led by Ulrich von Andrian, HMS associate professor of pathology at the Center for Blood Research, has shown that these chemical attractants can also travel to microvessels in the lymph node where they stick like flies to the tacky endothelial lining. There they flag down monocytes racing through the circulation.
Ulrich von Andrian has discovered a "remote control" mechanism that cells at a wound use to alert the nearest lymph node and initiate an immune response. Photo by Pam Murray
The study, published in the November
Journal of Experimental Medicine solved the mystery of how events at a distant site, in the skin, for example, shape the immune response in a lymph node, sometimes thousands of cell lengths away. Using a special intravital microscopy system, von Andrian recorded adhesive interactions between a single leukocyte and the endothelial wall, in real time, on location, providing perhaps the most realistic glimpse of how the immune system operates.
Von Andrian and Barrett Rollins, HMS associate professor of medicine at Dana-Farber, used a strain of knockout mice deficient in one chemokine, monocyte chemotactic protein-1 (MCP-1) to prove that this molecule was critical to lure monocytes to the inflamed lymph node. Further experiments showed that MCP-1 was produced at the wound and then swept to the lymph node via incoming branches of the lymph system. There, it bound to the microvessels.
The researchers also tracked the movement of the monocyte. Dan Littman of NYU provided a mouse strain with a green fluorescent protein (GFP) gene knocked into a locus specifically expressed in monocytes. After injecting peripheral blood cells from these mice into a second wild-type mouse, the fluorescent subpopulation could be monitored in much the same way that radiocollared animals are tracked in nature. This was a technically difficult experiment, not only because the monocyte is a rare species, but also because only a small portion of these cells were of interest: the ones involved in homing. GFP-positive cells homed from the blood to an inflamed lymph node via the same microvessels that bound MCP-1.
--Anne Mahon
Copyright 2001 by the President and Fellows of Harvard College
