Neuronal MCP-1 expression in response to remote nerve injury.
Direct injury of the brain is followed by inflammatory responses regulated by cytokines and chemoattractants secreted from resident glia and invading cells of the peripheral immune system. In contrast, after remote lesion of the central nervous system, exemplified here by peripheral transection or crush of the facial and hypoglossal nerve, the locally observed inflammatory activation is most likely triggered by the damaged cells themselves, that is, the injured neurons. The authors investigated the expression of the chemoattractants monocyte chemoattractant protein MCP-1, regulation on activation normal T-cell expressed and secreted (RANTES), and interferon-gamma inducible protein IP10 after peripheral nerve lesion of the facial and hypoglossal nuclei. In situ hybridization and immunohistochemistry revealed an induction of neuronal MCP-1 expression within 6 hours postoperation, reaching a peak at 3 days and remaining up-regulated for up to 6 weeks. MCP-1 expression was almost exclusively confined to neurons but was also present on a few scattered glial cells. The authors found no alterations in the level of expression and cellular distribution of RANTES or IP10, which were both confined to neurons. Protein expression of the MCP-1 receptor CCR2 did not change. MCP-1, expressed by astrocytes and activated microglia, has been shown to be crucial for monocytic, or T-cell chemoattraction, or both. Accordingly, expression of MCP-1 by neurons and its corresponding receptor in microglia suggests that this chemokine is involved in neuron and microglia interaction.
Flügel
A
A
Department of Neuroimmunology, Max-Planck-Institute of Neurobiology, Martinsried, Germany.
Hager
G
G
Horvat
A
A
Spitzer
C
C
Singer
G M
GM
Graeber
M B
MB
Kreutzberg
G W
GW
Schwaiger
F W
FW
D000818:Animals; D019771:Axotomy; D001921:Brain / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000032:analysis / Q000235:genetics*; D018946:Chemokine CCL5 / Q000235:genetics; D005154:Facial Nerve / Q000378:metabolism*; D007839:Functional Laterality; D005786:Gene Expression Regulation; D007002:Hypoglossal Nerve / Q000378:metabolism; D061228:Hypoglossal Nerve Injuries; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008869:Microtubule-Associated Proteins / Q000032:analysis; D009474:Neurons / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D018121:Receptors, Cytokine / Q000032:analysis / Q000235:genetics
D018932:Chemokine CCL2; D018946:Chemokine CCL5; C104577:IP10-Mig receptor; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; D018121:Receptors, Cytokine