The calcium-binding proteins S100A8 and S100A9 initiate the early inflammatory program in injured peripheral nerves.

J Biol Chem

the Department of Anesthesiology, University of California, San Diego, La Jolla, California 92093, the Veterans Affairs San Diego Healthcare System, La Jolla, California 92037,

Published: May 2015

To shed light on the early immune response processes in severed peripheral nerves, we performed genome-wide transcriptional profiling and bioinformatics analyses of the proximal (P, regenerating) and distal (D, degenerating) nerve stumps on day 1 in the sciatic nerve axotomy model in rats. Multiple cell death-related pathways were activated in the degenerating D stump, whereas activation of the cytoskeletal motility and gluconeogenesis/glycolysis pathways was most prominent in the P stump of the axotomized nerve. Our bioinformatics analyses also identified the specific immunomodulatory genes of the chemokine, IL, TNF, MHC, immunoglobulin-binding Fc receptor, calcium-binding S100, matrix metalloproteinase, tissue inhibitor of metalloproteinase, and ion channel families affected in both the P and D segments. S100a8 and S100a9 were the top up-regulated genes in both the P and D segments. Stimulation of cultured Schwann cells using the purified S100A8/A9 heterodimer recapitulated activation of the myeloid cell and phagocyte chemotactic genes and pathways, which we initially observed in injured nerves. S100A8/A9 heterodimer injection into the intact nerve stimulated macrophage infiltration. We conclude that, following peripheral nerve injury, an immediate acute immune response occurs both distal and proximal to the lesion site and that the rapid transcriptional activation of the S100a8 and S100a9 genes results in S100A8/A9 hetero- and homodimers, which stimulate the release of chemokines and cytokines by activated Schwann cells and generate the initial chemotactic gradient that guides the transmigration of hematogenous immune cells into the injured nerve.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4416877PMC
http://dx.doi.org/10.1074/jbc.M114.622316DOI Listing

Publication Analysis

Top Keywords

s100a8 s100a9
12
peripheral nerves
8
immune response
8
bioinformatics analyses
8
schwann cells
8
s100a8/a9 heterodimer
8
nerve
6
calcium-binding proteins
4
proteins s100a8
4
s100a9 initiate
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!