PMID- 9671983 OWN - NLM STAT- MEDLINE DCOM- 19980924 LR - 20220309 IS - 0360-4012 (Print) IS - 0360-4012 (Linking) VI - 53 IP - 2 DP - 1998 Jul 15 TI - Monocyte chemoattractant protein 1 is responsible for macrophage recruitment following injury to sciatic nerve. PG - 260-7 AB - Following injury to the peripheral nervous system, circulating monocytes/macrophages are recruited to the damaged tissue, where they play vital roles during both nerve degeneration and subsequent regeneration. Monocyte chemoattractant protein-1 (MCP-1), a member of the C-C or beta-chemokine family, is a powerful leukocyte recruitment/activation factor that is relatively specific for monocytes/macrophages. Because these are the predominant leukocyte type recruited by injured nerve, we hypothesized that upregulation of MCP-1 expression is involved in recruitment of these cells. Indeed, assay of steady-state levels of MCP-1 mRNA in rat sciatic nerve during tellurium-induced primary demyelination indicated up-regulation of this chemokine with a peak after 3 days of tellurium exposure, preceding the peak of accumulation of phagocytic macrophages (assayed as lysozyme mRNA levels) by 6 days. Increasing levels of MCP-1 mRNA expression, induced by increasing levels of tellurium exposure, resulted in corresponding increases in subsequent recruitment of macrophages. In situ hybridization suggested that MCP-1 mRNA was localized in Schwann cells. No expression of MIP-2, which is a C-X-C or alpha-chemokine that is specific for recruitment of neutrophils, was detected, consistent with the lack of recruitment of significant numbers of these cells. In addition, we also investigated the response seen following nerve transection (axonal degeneration and secondary demyelination with no subsequent regeneration) and nerve crush (degeneration followed by regeneration). In these latter two nerve injury models, there was also a marked, early up-regulation of MCP-1 mRNA, with a time course that is compatible with a role for this chemokine in macrophage recruitment. We conclude that MCP-1 is involved in recruiting monocytes/macrophages to injured peripheral nerve and that the specificity of leukocyte types recruited results from specificity of chemokine production. FAU - Toews, A D AU - Toews AD AD - Department of Biochemistry and Biophysics, Neuroscience Center, University of North Carolina, Chapel Hill 27599-7250, USA. arrel@css.unc.edu FAU - Barrett, C AU - Barrett C FAU - Morell, P AU - Morell P LA - eng GR - ES-01104/ES/NIEHS NIH HHS/United States GR - HD-03110/HD/NICHD NIH HHS/United States GR - NS-11615/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Neurosci Res JT - Journal of neuroscience research JID - 7600111 RN - 0 (Chemokine CCL2) RN - 0 (RNA, Messenger) RN - NQA0O090ZJ (Tellurium) SB - IM MH - Animals MH - Blotting, Northern MH - Chemokine CCL2/biosynthesis/*physiology MH - Demyelinating Diseases/chemically induced/pathology MH - Immunohistochemistry MH - In Situ Hybridization MH - Macrophages/metabolism/pathology/*physiology MH - Male MH - Nerve Crush MH - RNA, Messenger/biosynthesis MH - Rats MH - Rats, Sprague-Dawley MH - Sciatic Nerve/*injuries MH - Tellurium/toxicity EDAT- 1998/07/22 02:14 MHDA- 2000/06/20 09:00 CRDT- 1998/07/22 02:14 PHST- 1998/07/22 02:14 [pubmed] PHST- 2000/06/20 09:00 [medline] PHST- 1998/07/22 02:14 [entrez] AID - 10.1002/(SICI)1097-4547(19980715)53:2<260::AID-JNR15>3.0.CO;2-A [pii] AID - 10.1002/(SICI)1097-4547(19980715)53:2<260::AID-JNR15>3.0.CO;2-A [doi] PST - ppublish SO - J Neurosci Res. 1998 Jul 15;53(2):260-7. doi: 10.1002/(SICI)1097-4547(19980715)53:2<260::AID-JNR15>3.0.CO;2-A.