Presence and activation of pro-inflammatory macrophages are associated with CRYAB expression in vitro and after peripheral nerve injury

Journal of Neuroinflammation

Ariana Frederick¹  Kunal Kapoor¹  Shalina S. Ousman²  Vahid Hoghooghi³  Kathleen M. Hagen³  Erin-Mai F. Lim³  Trisha M. Finlay³ 

[1] Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, 3330 Hospital Drive N.W., Heritage Medical Research Building, T2N 4N1, Calgary, Alberta, Canada;Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, 3330 Hospital Drive N.W., Heritage Medical Research Building, T2N 4N1, Calgary, Alberta, Canada;Department of Cell Biology & Anatomy, Hotchkiss Brain Institute, University of Calgary, 3330 Hospital Drive N.W., Heritage Medical Research Building, T2N 4N1, Calgary, Alberta, Canada;Department of Neuroscience, Hotchkiss Brain Institute, University of Calgary, 3330 Hospital Drive N.W., Heritage Medical Research Building, T2N 4N1, Calgary, Alberta, Canada;

关键词: Peripheral nervous system;    Peripheral nerve injury;    Macrophages;    Pro-inflammatory;    CRYAB;    AlphaB-crystallin;    Cytokines;    Chemokines;   

DOI  :  10.1186/s12974-021-02108-z

来源: Springer

【 摘 要 】

BackgroundInflammation constitutes both positive and negative aspects to recovery following peripheral nerve injury. Following damage to the peripheral nervous system (PNS), immune cells such as macrophages play a beneficial role in creating a supportive environment for regrowing axons by phagocytosing myelin and axonal debris. However, a prolonged inflammatory response after peripheral nerve injury has been implicated in the pathogenesis of negative symptoms like neuropathic pain. Therefore, the post-injury inflammation must be carefully controlled to prevent secondary damage while allowing for regeneration. CRYAB (also known as alphaB-crystallin/HSPB5) is a small heat shock protein that has many protective functions including an immunomodulatory role in mouse models of multiple sclerosis, spinal cord injury, and stroke. Because its expression wanes and rebounds in the early and late periods respectively after PNS damage, and CRYAB null mice with sciatic nerve crush injury display symptoms of pain, we investigated whether CRYAB is involved in the immune response following PNS injury.MethodsSciatic nerve crush injuries were performed in age-matched Cryab knockout (Cryab−/−) and wildtype (WT) female mice. Nerve segments distal to the injury site were processed by immunohistochemistry for macrophages and myelin while protein lysates of the nerves were analyzed for cytokines and chemokines using Luminex and enzyme-linked immunosorbent assay (ELISA). Peritoneal macrophages from the two genotypes were also cultured and polarized into pro-inflammatory or anti-inflammatory phenotypes where their supernatants were analyzed for cytokines and chemokines by ELISA and protein lysates for macrophage antigen presenting markers using western blotting.ResultsWe report that (1) more pro-inflammatory CD16/32+ macrophages are present in the nerves of Cryab−/− mice at days 14 and 21 after sciatic nerve crush-injury compared to WT counterparts, and (2) CRYAB has an immunosuppressive effect on cytokine secretion [interleukin (IL)-β, IL-6, IL-12p40, tumor necrosis factor (TNF)-α] from pro-inflammatory macrophages in vitro.ConclusionsCRYAB may play a role in curbing the potentially detrimental pro-inflammatory macrophage response during the late stages of peripheral nerve regeneration.

【 授权许可】

CC BY