Polyethylene glycol-fusion repair of sciatic allografts in female rats achieves immunotolerance via attenuated innate and adaptive responses.
RRID:AB_10917271
RRID:AB_1141521
RRID:AB_1210523
RRID:AB_2315387
RRID:AB_2341188
RRID:AB_2556545
RRID:AB_2556548
RRID:AB_306429
RRID:AB_531793
RRID:AB_566872
RRID:AB_567369
RRID:AB_791151
RRID:RGD_737903
RRID:SCR_001620
RRID:SCR_002285
RRID:SCR_002760
RRID:SCR_002798
RRID:SCR_003070
RRID:SCR_016517
Schwann cell
T cell
Wallerian degeneration
allograft rejection
axotomy
chemokines
cytokines
immune response
macrophage
nerve repair
polyethylene glycol
transplantation
Journal
Journal of neuroscience research
ISSN: 1097-4547
Titre abrégé: J Neurosci Res
Pays: United States
ID NLM: 7600111
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
05
09
2019
revised:
31
07
2020
accepted:
11
08
2020
pubmed:
16
9
2020
medline:
18
9
2021
entrez:
15
9
2020
Statut:
ppublish
Résumé
Ablation/segmental loss peripheral nerve injuries (PNIs) exhibit poor functional recovery due to slow and inaccurate outgrowth of regenerating axons. Viable peripheral nerve allografts (PNAs) as growth-guide conduits are immunologically rejected and all anucleated donor/host axonal segments undergo Wallerian degeneration. In contrast, we report that ablation-type sciatic PNIs repaired by neurorrhaphy of viable sciatic PNAs and a polyethylene glycol (PEG)-fusion protocol using PEG immediately restored axonal continuity for many axons, reinnervated/maintained their neuromuscular junctions, and prevented much Wallerian degeneration. PEG-fused PNAs permanently restored many sciatic-mediated behaviors within 2-6 weeks. PEG-fused PNAs were not rejected even though host/donors were neither immunosuppressed nor tissue-matched in outbred female Sprague Dawley rats. Innate and adaptive immune responses to PEG-fused sciatic PNAs were analyzed using electron microscopy, immunohistochemistry, and quantitative reverse transcription polymerase chain reaction for morphological features, T cell and macrophage infiltration, major histocompatibility complex (MHC) expression, apoptosis, expression of cytokines, chemokines, and cytotoxic effectors. PEG-fused PNAs exhibited attenuated innate and adaptive immune responses by 14-21 days postoperatively, as evidenced by (a) many axons and cells remaining viable, (b) significantly reduced infiltration of cytotoxic and total T cells and macrophages, (c) significantly reduced expression of inflammatory cytokines, chemokines, and MHC proteins, (d) consistently low apoptotic response. Morphologically and/or biochemically, PEG-fused sciatic PNAs often resembled sciatic autografts or intact sciatic nerves. In brief, PEG-fused PNAs are an unstudied, perhaps unique, example of immune tolerance of viable allograft tissue in a nonimmune-privileged environment and could greatly improve the clinical outcomes for PNIs relative to current protocols.
Substances chimiques
Polyethylene Glycols
3WJQ0SDW1A
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
2468-2495Subventions
Organisme : NIH HHS
ID : R01 CA31534
Pays : United States
Organisme : NIH HHS
ID : R01 NS081063
Pays : United States
Organisme : Cancer Prevention and Research Institute of Texas
ID : RP100612
Pays : International
Organisme : Cancer Prevention and Research Institute of Texas
ID : RP120348
Pays : International
Organisme : NIH HHS
ID : R01 CA31534
Pays : United States
Organisme : NIH HHS
ID : R01 NS081063
Pays : United States
Informations de copyright
© 2020 Wiley Periodicals LLC.
Références
Abrahimi, P., Liu, R., & Pober, J. S. (2015). Blood vessels in allotransplantation. American Journal of Transplantation, 15, 1748-1754.
Amanzada, A., Malik, I. A., Blaschke, M., Khan, S., Rahman, H., Ramadori, G., & Moriconi, F. (2013). Identification of CD68(+) neutrophil granulocytes in in vitro model of acute inflammation and inflammatory bowel disease. International Journal of Clinical and Experimental Pathology, 6(4), 561-570.
Ansselin, A. D., & Pollard, J. D. (1990). Immunopathological factors in peripheral nerve allograft rejection: Quantification of lymphocyte invasion and major histocompatibility complex expression. Journal of the Neurological Sciences, 96, 75-88.
Beltran, M. J., Burns, T. C., Eckel, T. T., Potter, B. K., Wenke, J. C., Hsu, J. R., & Skeletal Trauma Research Consortium (STReC). (2012). Fate of combat nerve injury. Journal of Orthopaedic Trauma, 26, e198-e203.
Bittner, G., Ghergherehchi, C., Michelle, M., Sengelaub, D., Trevino, R., & Shores, J. (2019). Salomone et al did not induce PEG-fusion repair of rat facial nerves. Head & Neck, 41(10), 3737-3739.
Bittner, G. D., Keating, C. P., Kane, J. R., Britt, J. M., Spaeth, C. S., Fan, J. D., … Schallert, T. (2012). Rapid, effective, and long-lasting recovery produced by microsutures, methylene blue, and polyethylene glycol after completely cutting rat sciatic nerves. Journal of Neuroscience Research, 90, 967-980.
Bittner, G. D., Sengelaub, D. R., & Ghergherehchi, C. L. (2017). Conundrums and confusions regarding how PEG-fusion produces excellent behavioral recovery after peripheral nerve injuries. Neural Regeneration Research, 13(1), 53-57.
Bittner, G. D., Sengelaub, D. R., Trevino, R. C., Peduzzi, J. D., Mikesh, M., Ghergherehchi, C. L., … Thayer, W. P. (2016). The curious ability of PEG-fusion technologies to restore lost behaviors after nerve severance. Journal of Neuroscience Research, 94, 207-230.
Brower, M., Grace, M., Kotz, C. M., & Koya, V. (2015). Comparative analysis of growth characteristics of Sprague Dawley rats obtained from different sources. Laboratory Animal Research, 31(4), 166-173.
Brown, B. L., Asante, T., Welch, H. R., Sandelski, M. M., Drejet, S. M., Shah, K., … Walker, C. L. (2019). Functional and anatomical outcomes of facial nerve injury with application of polyethylene glycol in a rat model. JAMA Facial Plastic Surgery, 21(1), 61-68.
Brushart, T. M. (2011). Nerve repair. New York, NY: Oxford University Press.
Campbell, L., Saville, C. R., Murray, P. J., Cruickshank, S. M., & Hardman, M. J. (2013). Arginase 1 activity is required for cutaneous wound healing. Journal of Investigative Dermatology, 133, 2461-2470.
Campbell, W. W. (2008). Evaluation and management of peripheral nerve injury. Clinical Neurophysiology, 119(9), 1951-1965.
Carlton, J. M., & Goldberg, N. (1986). Quantitative integrated muscle function following reinnervation. Surgical Forum, 37, 611-612.
Choy, J. C. (2010). Granzymes and perforin in solid organ transplant rejection. Cell Death and Differentiation, 17, 567-576.
Cross, J. D., Ficke, J. R., Hsu, J. R., Masini, B. D., & Wenke, J. C. (2011). Battlefield orthopaedic injuries cause the majority of long-term disabilities. Journal of American Academy of Orthopaedic Surgeons, 19(Suppl. 1), S1-S7.
Davies, A. J., Kim, H. W., Gonzalez-Cano, R., Choi, J., Back, S. K., Roh, S. E., … Oh, S. B. (2019). Natural killer cells degenerate intact sensory afferents following nerve injury. Cell, 176, 716-728.
de Medinaceli, L. (1995). Interpreting nerve morphometry data after experimental traumatic lesions. Journal of Neuroscience Methods, 58, 29-37.
de Medinaceli, L., Freed, W. J., & Wyatt, R. J. (1982). An index of the functional condition of rat sciatic nerve based on measurements made from walking tracks. Experimental Neurology, 77, 634-643.
DeFrancesco-Lisowitz, A., Lindborg, J. A., Niemi, J. P., & Zigmond, R. E. (2015). The neuroimmunology of degeneration and regeneration in the peripheral nervous system. Neuroscience, 302, 174-203.
Deshmane, S. L., Kremlev, S., Amini, S., & Sawaya, B. E. (2009). Monocyte chemoattractant protein-1 (MCP-1): An overview. Journal of Interferon and Cytokine Research, 29(6), 313-326.
Evans, P. J., Mackinnon, S. E., Levi, A. D., Wade, J. A., Hunter, D. A., Nakao, Y., & Midha, R. (1998). Cold preserved nerve allografts: Changes in basement membrane, viability, immunogenicity, and regeneration. Muscle and Nerve, 21(11), 1507-1522.
Evans, P. J., Midha, R., & Mackinnon, S. E. (1994). The peripheral nerve allograft: A comprehensive review of regeneration and neuroimmunology. Progress in Neurobiology, 43, 187-233.
Ferrar, C. A., Kupiec-Weglinski, J. W., & Sacks, S. H. (2013). The innate immune system and transplantation. Cold Spring Harbor Perspectives in Medicine, 3, a015479.
Friedman, O., Carmel, N., Sela, M., Jabal, A. A., Inbal, A., Hamou, M. B., … Shani, N. (2017). Immunological and inflammatory mapping of vascularized composite allograft processes in a rat model. PLoS ONE, 12(7), e0181507.
Gaudet, A. D., Popovich, P. G., & Ramer, M. S. (2011). Wallerian degeneration: Gaining perspective on inflammatory events after peripheral nerve injury. Journal of Neuroinflammation, 8, 110.
Ghergherehchi, C. L., Mikesh, M., Sengelaub, D. R., Jackson, D. M., Smith, T., Nguyen, J., … Bittner, G. D. (2019). Polyethylene glycol (PEG) and other bioactive solutions with neurorraphy for rapid and dramatic repair of peripheral nerve lesions by PEG-fusion. Journal of Neuroscience Methods, 314, 1-12.
Ghergherehchi, C. L., Sengelaub, D. R., Mikesh, M., & Bittner, G. D. (2019). Alterations in spinal connectivity and remodeling of motoneuron dendritic morphology after sciatic nerve transection with polyethylene glycol axon fusion repair. PLoS ONE, 14(10), e0223443.
Giraud, S., Claire, B., Eugene, M., Debre, P., Richard, F., & Barrou, B. (2007). A new preservation solution increases islet yield and reduced graft immunogenicity in pancreatic islet transplantation. Transplantation, 83(10), 1397-1400.
Goping, I. S., Barry, M., Liston, P., Sawchuk, T., Constantinescu, G., Michalak, K. M., … Bleackley, R. C. (2003). Granzyme B-induced apoptosis requires both direct caspase activation and relief of caspase inhibition. Immunity, 18(13), 355-365.
Gottfried, E., Kunz-Schughart, L. A., Weber, A., Rehli, M., Peuker, A., Müller, A., … Kreutz, M. (2008). Expression of CD68 in non-myeloid cell types. Scandinavian Journal of Immunology, 67(5), 453-463.
Grinspan, J. B., Marchionni, M. A., Reeves, M., Coulaloglou, M., & Scherer, S. S. (1996). Axonal interactions, regulate Schwann cell apoptosis in developing peripheral nerve: Neuregulin receptors and the role of neuregulins. Journal of Neuroscience, 16(19), 6107-6118.
Jessen, K. R., Mirsky, R., & Lloyd, A. C. (2015). Schwann cells: Development and role in nerve repair. Cold Spring Harbor Perspectives in Medicine, 7, a020487.
Jiang, H., Wynn, C., Pan, F., Ebbs, A., Erickson, L. M., & Kobayashi, M. (2002). Tacrolimus and cyclosporine differ in their capacity to overcome ongoing allograft rejection as a result of their differential abilities to inhibit interleukin-10 production. Transplantation, 73(11), 1808-1817.
Kaiserling, E., Xiao, J. C., Ruck, P., & Horny, H. P. (1993). Aberrant expression of macrophage-associated antigens (CD68 and Ki-M1P) by Schwann cells in reactive and neoplastic neural tissue. Light- and electron-microscopic findings. Modern Pathology, 6(4), 463-468.
Kang, H., Tian, L., Son, Y. J., Zuo, Y., Procaccino, D., Love, F., … Thompson, W. (2007). Regulation of the intermediate filament protein nestin at rodent neuromuscular junctions by innervation and activity. Journal of Neuroscience, 27(22), 5948-5957.
Kennedy, A. D., & DeLeo, F. R. (2009). Neutrophil apoptosis and the resolution of infection. Immunologic Research, 43, 23-61.
Kuhlmann, T., Bitsch, A., Stadelmann, C., Siebert, H., & Brück, W. (2001). Macrophages are eliminated from the injured peripheral nerve via apoptosis and circulation to regional lymph nodes and the spleen. Journal of Neuroscience, 21(10), 3401-3408.
Kyluik-Price, D. L., & Scott, M. D. (2016). Effects of methoxypoly (ethylene glycol) mediated immunocamouflage on leukocyte surface marker detection, cell conjugation, activation and alloproliferation. Biomaterials, 74, 167-177.
Lassner, F., Schaller, E., Steinhoff, G., Wonigeit, K., Walter, G. F., & Berger, A. (1989). Cellular mechanisms of rejection and regeneration in peripheral nerve allografts. Transplantation, 48, 386-392.
Le, Y., & Scott, M. (2010). Immunocamouflage: The biophysical basis of immunoprotection by grafted methoxypoly(ethylene glycol) (mPEG). Acta Biomaterialia, 6(7), 2631-2641.
Lindborg, J. A., Mack, M., & Zigmond, R. E. (2017). Neutrophils are critical for myelin removal in a peripheral nerve injury model of Wallerian degeneration. Journal of Neuroscience, 37(43), 10258-10277.
Lisak, R. P., Bealmear, B., & Benjamins, J. A. (2016). Schwann cell differentiation inhibits interferon-gamma induction of expression of major histocompatibility complex class II and intercellular adhesion molecule-1. Journal of Neuroimmunology, 295, 93-99.
Livak, K. J., & Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method. Methods, 25, 402-408.
Mackinnon, S. E., Midha, R., Bain, J., Hunter, D., & Wade, J. (1992). An assessment of regeneration across peripheral nerve allografts in rats receiving short courses of cyclosporin A immunosuppression. Neuroscience, 46(3), 585-593.
Mackinnon, S. E., Vaishali, D. B., Novak, C. B., & Trulock, E. P. (2001). Clinical outcome following nerve allograft transplantation. Plastic and Reconstructive Surgery, 107, 1419-1429.
Madsen, D. H., Leonard, D., Masedunskas, A., Moyer, A., Jürgensen, H. J., Peters, D. E., … Bugge, T. H. (2013). M2-like macrophages are responsible for collagen degradation through a mannose receptor-mediated pathway. Journal of Cell Biology, 202(6), 951-966.
Magill, C. K., Moore, A. M., Borschel, G. H., & Mackinnon, S. E. (2010). A new model for facial nerve research. Archives of Facial Plastic Surgery, 12(5), 315-320.
Mata, M., Alessi, D., & Fink, D. J. (1990). S100 is preferentially distributed in myelin-forming Schwann cells. Journal of Neurocytology, 19, 432-442.
McWhorter, F. Y., Davis, C. T., & Liu, W. F. (2015). Physical and mechanical regulation of macrophage phenotype and function. Cellular and Molecular Life Sciences, 72, 1303-1316.
Metzemaekers, M., Venheule, V., Janssens, R., Struyf, S., & Proost, P. (2018). Overview of the mechanisms that may contribute to the non-redundant activities of interferon-inducible CXC chemokine receptor 3 ligands. Frontiers in Immunology, 8, 1970. https://doi.org/10.3389/fimmu.2017.01970
Mika, S. E., & Stepnowski, P. (2016). Current methods of the analysis of immunosuppressive agents in clinical materials: A review. Journal of Pharmaceutical and Biomedical Analysis, 127, 207-231.
Mikesh, M., Ghergherehchi, C. L., Hastings, R. L., Ali, A., Rahesh, S., Jagannath, K., … Bittner, G. D. (2018). Polyethylene glycol solutions rapidly restore and maintain axonal continuity, neuromuscular structures, and behaviors lost after sciatic nerve transections in female rats. Journal of Neuroscience Research, 96(7), 1223-1242. https://doi.org/10.1002/jnr.24225
Mikesh, M. F., Ghergherehchi, C. L., Rahesh, S., Jagannath, K., Ali, A., Sengelaub, D. R., … Bittner, G. D. (2018). Polyethylene glycol treated allografts not tissue matched nor immunosuppressed rapidly repair sciatic nerve gaps, maintain neuromuscular junctions, and restore voluntary behaviors in female rats. Journal of Neuroscience Research, 96(7), 1243-1264.
Mimouni-Rongy, M., White, J. H., Weinstein, D. E., Desbarats, J., & Almazan, G. (2011). Fas ligand acts as a counter-receptor in Schwann cells and induces the secretion of bioactive nerve growth factor. Journal of Neuroimmunology, 230, 17-25.
Mitsuhashi, N., Wu, G. D., Kearns-Jonker, M., Cramer, D. V., Starnes, V. A., & Barr, M. L. (2007). Rat chemokine CXCL11: Structure, tissue distribution, function and expression in cardiac transplantation models. Molecular and Cellular Biochemistry, 296(1-2), 1-9.
Moreau, A., Varey, E., Anegon, I., & Cuturi, M. C. (2013). Effector mechanisms of rejection. Cold Spring Harbor Perspectives in Medicine, 3, a015461.
Murphy, K., & Weaver, C. (2017). Janeway’s immunobiology (9th ed.). New York, NY: Garland Science.
Murray, P. J. (2017). Macrophage polarization. Annual Review of Physiology, 79, 541-566.
Oltean, M., Joshi, M., Björkman, E., Oltean, S., Casselbrant, A., Herlenius, G., & Olausson, M. (2012). Intraluminal polyethylene glycol stabilizes tight junctions and improves intestinal preservation in the rat. American Journal of Transplantation, 12(8), 2044-2051.
Pollard, J. D., & Fitzpatrick, L. (1973). An ultrastructural comparison of peripheral nerve allografts and autografts. Acta Neuropathologica, 23, 152-165.
Raffe, M. R. (1985). Principles of peripheral nerve repair. Textbook of Small Animal Orthopaedics, Chapter 65. Ithaca, NY: International Veterinary Information Service.
Riley, D. C., Bittner, G. D., Mikesh, M., Cardwell, N. L., Pollins, A. C., Ghergherehchi, C. L., … Thayer, W. P. (2015). Polyethylene glycol-fused allografts produce rapid behavioral recovery after ablation of sciatic nerve segments. Journal of Neuroscience Research, 93, 572-583.
Roballo, K. C. S., & Bushman, J. (2019). Evaluation of the host immune response and functional recovery in peripheral nerve autografts and allografts. Transplant Immunology, 53, 61-71.
Robinson, G. A., & Madison, R. D. (2016). Polyethylene glycol fusion prevents reinnervation accuracy in rat peripheral nerve. Journal of Neuroscience Research, 94(7), 634-636.
Rosenberg, A. F., Wolman, M. A., Franzini-Armstrong, C., & Granato, M. (2012). In vivo nerve-macrophage interactions following peripheral nerve injury. Journal of Neuroscience, 32(11), 3898-3909.
Sachanandani, N. F., Pothula, A., & Tung, T. H. (2014). Nerve gaps. Plastic and Reconstructive Surgery, 133(2), 313-319.
Sasaki, Y., Ohsawa, K., Kanazawa, H., Kohsaka, S., & Imai, Y. (2001). Iba1 is an actin-cross-linking protein in macrophages/microglia. Biochemical and Biophysical Research Communications, 286(2), 292-297.
Schnickel, G. T., Bastani, S., Hsieh, G. R., Shefizadeh, A., Bhatia, R., Fishbein, M. C., … Ardehali, A. (2008). Combined CXCR3/CCR5 blockade attenuates acute and chronic rejection. Journal of Immunology, 180(7), 4714-4721.
Schroder, K., Hertzog, P. J., Ravasi, T., & Hume, D. A. (2004). Interferon-γ: An overview of signals, mechanisms and functions. Journal of Leukocyte Biology, 75, 163-189.
Schwartz, R. H. (2003). T cell anergy. Annual Review of Immunology, 21, 305-334.
Shaefer, A., & Hordijk, P. J. (2015). Cell-stiffness-induced mechanosignaling-A key driver of leukocyte transendothelial migration. Journal of Cell Science, 128, 2221-2230.
Smith, I. W., Mikesh, M., Lee, Y., & Thompson, W. J. (2013). Terminal Schwann cells participate in the competition underlying neuromuscular synapse elimination. Journal of Neuroscience, 33, 17724-17736.
Sojka, D. K., & Fowell, D. J. (2011). Regulatory T cells inhibit acute IFN-γ synthesis without blocking T-helper cell type 1 (Th1) differentiation via a compartmentalized requirement for IL-10. Proceedings of the National Academy of Sciences of the United States of America, 108(45), 18336-18341.
Solomone, R., Luiz Jácomo, A.,Bona do Nascimento, S., Lezirovitz, K., Carneiro Hojaij, F.,Juliana Zebeu Rossi Costa, H., & Ferreira Bento, R. (2018). Polyethylene glycol fusion associated with antioxidants: A new promise in the treatment of traumatic facial paralysis. Head & Neck, 40, 1489-1497.
Thuillier, R., Giraud, S., Favreau, F., Goijon, J. M., Desurmont, T., Eugene, M., … Hauet, T. (2011). Improving long-term outcome in allograft transplantation: Role of ionic composition and polyethylene glycol. Transplantation, 91, 605-614.
Turner, M. D., Nedjai, B., Hurst, T., & Pennington, D. J. (2014). Cytokines and chemokines: At the crossroads of cell signaling and inflammatory disease. Biochimica et Biophysica Acta, 1843(11), 2563-2582.
Varejao, A. S., Meek, M. F., Ferreira, A. J., Patricio, A. J., & Cabrita, A. M. (2001). Functional evaluation of peripheral nerve regeneration in the rat: Walking track analysis. Journal of Neuroscience Methods, 68(1), 1-9.
Vargas, S. A., & Bittner, G. D. (2019). Natural mechanisms and artificial PEG-induced mechanism that repair traumatic damage to the plasmalemma in eukaryotes. Current Topics in Membranes, 84, 129-167.
Zheng, T. S., Schlosser, S. F., Dao, T., Hingorani, R., Crispe, I. N., Boyer, J. L., & Flavell, R. A. (1998). Caspase 3 controls both cytoplasmic and nuclear events associated with Fas-mediated apoptosis in vivo. Proceedings of the National Academy of Sciences of the United States of America, 95(23), 13618-13623.