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Denervated Schwann Cells Attract Macrophages by Secretion of Leukemia Inhibitory Factor (LIF) and Monocyte Chemoattractant Protein-1 in a Process Regulated by Interleukin-6 and LIF

Tofaris, George K. and Patterson, Paul H. and Jessen, Kristjan R. and Mirsky, Rhona (2002) Denervated Schwann Cells Attract Macrophages by Secretion of Leukemia Inhibitory Factor (LIF) and Monocyte Chemoattractant Protein-1 in a Process Regulated by Interleukin-6 and LIF. Journal of Neuroscience, 22 (15). pp. 6696-6703. ISSN 0270-6474. PMCID PMC6758146. doi:10.1523/jneurosci.22-15-06696.2002. https://resolver.caltech.edu/CaltechAUTHORS:20160212-092208717

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Abstract

Injury to peripheral nerves results in the infiltration of immune cells, which remove axonal- and myelin-derived material. Schwann cells could play a key role in this process by regulating macrophage infiltration. We show here that medium conditioned by primary denervated Schwann cells or the Schwannoma cell line RN22 produces chemotactic activity for macrophages. The presence of blocking antibodies to macrophage chemoattractant protein-1 (MCP-1) or leukemia inhibitory factor (LIF) reduced this activity to ∼35 and 65% of control levels, respectively, and only 15% remained in the presence of both antibodies. The presence of chemotactic LIF in Schwann cell-conditioned medium was confirmed by using cells fromlif−/− mice. Although interleukin-6 (IL-6) is not itself a chemotactic factor, we found that medium fromil-6−/− nerves showed only 40% of the activity secreted by wild-type nerves. Furthermore, IL-6 rapidly induced LIF mRNA in primary Schwann cells, and LIF rapidly induced MCP-1 mRNA expression. Treatment of RN22 Schwannoma cells with IL-6 or LIF enhanced the secretion of the chemotactic activity of these cells. These observations show that Schwann cells attract macrophages by secreting MCP-1 and LIF. They also provide evidence for an autocrine-signaling cascade involving IL-6, LIF, and MCP-1, which amplifies the Schwann cell-derived chemotactic signals gradually, in agreement with the delayed entry of macrophages to injured nerves.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1523/jneurosci.22-15-06696.2002DOIArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/pmc6758146/PubMed CentralArticle
Additional Information:© 2002 Society for Neuroscience. For the first six months after publication SfN’s license will be exclusive. Beginning six months after publication the Work will be made freely available to the public on SfN’s website to copy, distribute, or display under a Creative Commons Attribution 4.0 International (CC BY 4.0) license (https://creativecommons.org/licenses/by/4.0/). Received Dec. 26, 2001; revised May 6, 2002; accepted May 24, 2002. This work was supported by awards to G.K.T. from the Wolfson Foundation, the Howard Hughes Medical Institute through a California Institute of Technology (Caltech) Summer Undergraduate Research Fellowship, SmithKline Beecham Pharmaceuticals, and Trinity College (Cambridge, UK). R.M. and K.R.J. are supported by the Wellcome Trust. The work at Caltech was supported by a grant to P.H.P. from the National Institute of Neurological Disorders and Stroke. We thank Soheila Sharghi Namini and Sarah Dickinson for technical assistance with conditioned medium preparation and Doreen McDowell and Debbie Bartram for administrative assistance.
Funders:
Funding AgencyGrant Number
Wolfson FoundationUNSPECIFIED
Caltech Summer Undergraduate Research Fellowship (SURF)UNSPECIFIED
SmithKline Beecham PharmaceuticalsUNSPECIFIED
Trinity College (Cambridge, UK)UNSPECIFIED
Wellcome TrustUNSPECIFIED
NIHUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Subject Keywords:chemotaxis; macrophage; leukemia inhibitory factor; interleukin 6; regeneration; neuropathy
Issue or Number:15
PubMed Central ID:PMC6758146
DOI:10.1523/jneurosci.22-15-06696.2002
Record Number:CaltechAUTHORS:20160212-092208717
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20160212-092208717
Official Citation:Denervated Schwann Cells Attract Macrophages by Secretion of Leukemia Inhibitory Factor (LIF) and Monocyte Chemoattractant Protein-1 in a Process Regulated by Interleukin-6 and LIF George K. Tofaris, Paul H. Patterson, Kristjan R. Jessen, and Rhona Mirsky The Journal of Neuroscience, 1 August 2002, 22(15):6696-6703
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:64458
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:19 Feb 2016 20:41
Last Modified:10 Nov 2021 23:31

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