The Calcium-binding Proteins S100A8 and S100A9 Initiate the Early Inflammatory Program in Injured Peripheral Nerves

Abstract

Background:In peripheral nerves, the initial immune response to injury influences regeneration. Results: S100a8 and S100a9 are the top induced genes in nerves post-injury. S100A8/A9 activate the chemotactic genes and pathways in Schwann cells and stimulate myeloid cell infiltration into the nerve. Conclusion: S100A8/A9 initiate immune cell transmigration into the nerve. Significance: S100A8/A9 are novel modulators of peripheral nerve injury.

Proteomic Analysis of Pelvic Autonomic Nerve in Nerve-sparing Radical Hysterectomy for Cervical Carcinoma

“…Proteins S100-A8 and A9 are presumed to be related to the pelvic autonomic nerve according to H&E and S100 stain for nerve fibres, as well as the review of HPA and literature (18). To our knowledge, immunohistochemical expression in the peripheral nerve has not been reported.…”

“…Protein S100-A8/9 complex leads to the following process. Immediately after injury, the chemokine-cytokine network is up-regulated in Schwann cells, and an initial chemotactic gradient is formed so that haematogenous immune cells are attracted to the site of injury (18).…”

Schwann cells participate in synapse elimination at the developing neuromuscular junction

“…In myasthenia gravis, tSCs send phagocytic processes to invade nerve terminals [44]; similarly, after the injection of myotoxins, tSCs send phagocytic processes to separate the nerve and muscle endplate [45,46]. Cellular damage, either from denervation or disease, can lead to the release of damage-associated molecular pattern molecules (DAMPs) [47–49]. In addition to being strong activators of the innate immune response, recent evidence supports a role of DAMPs in the activation of SCs through molecular pathways found in both immune cells and SCs, including pathways for toll-like receptors and cytokines [50,51].…”

Danger in the Intensive Care Unit

“…Furthermore, several S100 proteins are released after trauma. For example, S100A8 and S100A9 induce an inflammatory response after damage of the peripheral nerves (19). Interestingly, blunt trauma survivors demonstrate higher plasma S100A8/A9 level compared with nonsurvivors, suggesting a protective role of S100 proteins after trauma (66).…”