TY - JOUR T1 - Vesicle-Mediated Transport and Release of CCL21 in Endangered Neurons: A Possible Explanation for Microglia Activation Remote from a Primary Lesion JF - The Journal of Neuroscience JO - J. Neurosci. SP - 7548 LP - 7557 DO - 10.1523/JNEUROSCI.1019-05.2005 VL - 25 IS - 33 AU - Eiko K. de Jong AU - Ineke M. Dijkstra AU - Marjolein Hensens AU - Nieske Brouwer AU - Machteld van Amerongen AU - Robert S. B. Liem AU - Hendrikus W. G. M. Boddeke AU - Knut Biber Y1 - 2005/08/17 UR - http://www.jneurosci.org/content/25/33/7548.abstract N2 - Whenever neurons in the CNS are injured, microglia become activated. In addition to local activation, microglia remote from the primary lesion site are stimulated. Because this so-called secondary activation of microglia is instrumental for long-term changes after neuronal injury, it is important to understand how microglia activity is controlled. The remote activation of microglia implies that the activating signals are transported along neuronal projections. However, the identity of these signals has not yet been identified. It is shown here that glutamate-treated neurons rapidly express and release the chemokine CCL21. We also provide evidence that neuronal CCL21 is packed in vesicles and transported throughout neuronal processes to reach presynaptic structures. Chemotaxis assays show that functional CCL21 is released from endangered neurons and activate microglia via the chemokine receptor CXCR3. Based on these findings, we suggest that neuronal CCL21 is important in directed neuron-microglia signaling and that this communication could account for the remote activation of microglia, far distant from a primary lesion. ER -