Acute injury in the peripheral nervous system triggers an alternative macrophage response

Ydens, Elke; Cauwels, Anje; Asselbergh, Bob; Goethals, Sofie; Peeraer, Lieve; Lornet, Guillaume; Almeida-Souza, Le­onardo; Ginderachter, Jo A. Van; Timmerman, Vincent; Janssens, Sophie

doi:10.1186/1742-2094-9-176

Cited by 138 publications

(102 citation statements)

References 90 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Neutrophil inflammatory and anti-inflammatory subsets similarly exist; and, like macrophages (Ydens et al, 2012), their functions are modulated by cellular changes and cytokine fluctuations in the tissue environment (de Oliveira et al, 2016). However, minimal characterization of neutrophil activation states in the context of nerve injury has been done, which presents an uncharted avenue for further exploration.…”

Section: Discussionmentioning

confidence: 99%

“…Under homeostatic conditions, resident macrophages proliferate and phagocytose debris and apoptotic cells independently of immune cell recruitment (Mosser and Edwards, 2008;Hashimoto et al, 2013). Resident macrophages begin to proliferate 2 d after sciatic nerve injury and, along with Schwann cells, readily phagocytose myelin debris before the appearance of hematogenous macrophages at 3-4 d after injury Mueller et al, 2001;Hirata and Kawabuchi, 2002;Mueller et al, 2003;Ydens et al, 2012). Although we report that a combination of cells compensates for the loss of CCR2 ϩ macrophages in the Ccr2 Ϫ / Ϫ model, the data point to neutrophils as the most marked change relative to WT mice.…”

Section: Schwann Cells Play In Myelin Removal In the Ccr2mentioning

confidence: 99%

See 1 more Smart Citation

Neutrophils Are Critical for Myelin Removal in a Peripheral Nerve Injury Model of Wallerian Degeneration

2017

View full text Add to dashboard Cite

Wallerian degeneration (WD) is considered an essential preparatory stage to the process of axonal regeneration. In the peripheral nervous system, infiltrating monocyte-derived macrophages, which use the chemokine receptor CCR2 to gain entry to injured tissues from the bloodstream, are purportedly necessary for efficient WD. However, our laboratory has previously reported that myelin clearance in the injured sciatic nerve proceeds unhindered in the Ccr2Ϫ / Ϫ mouse model. Here, we extensively characterize WD in male Ccr2Ϫ / Ϫ mice and identify a compensatory mechanism of WD that is facilitated primarily by neutrophils. In response to the loss of CCR2, injured Ccr2 Ϫ / Ϫ sciatic nerves demonstrate prolonged expression of neutrophil chemokines, a concomitant extended increase in the accumulation of neutrophils in the nerve, and elevated phagocytosis by neutrophils. Neutrophil depletion substantially inhibits myelin clearance after nerve injury in both male WT and Ccr2 Ϫ / Ϫ mice, highlighting a novel role for these cells in peripheral nerve degeneration that spans genotypes.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Schwann Cells Play In Myelin Removal In the Ccr2mentioning

confidence: 99%

Neutrophils Are Critical for Myelin Removal in a Peripheral Nerve Injury Model of Wallerian Degeneration

2017

View full text Add to dashboard Cite

show abstract

“…39 Macrophages are vital in the regeneration of damaged nerves after injury to the central nervous system and peripheral nervous system and, although infiltrating sensory nerves present within endometriosis lesions are not damaged per se, they may experience a chemical milieu similar to inflammation in response to trauma. 40 In a mouse model of acute peripheral nerve injury, an alternative macrophage response was detected, 41 and this phenotype has been associated with a sterile inflammatory environment similar to endometriosis. We suggest that the reciprocal relationship between macrophages and nerves encourages innervation of endometriosis lesions.…”

Section: Endometriosis Is a Neuroinflammatory Disordermentioning

confidence: 99%

Estradiol Is a Critical Mediator of Macrophage-Nerve Cross Talk in Peritoneal Endometriosis

Greaves

Temp

Esnal-Zufiurre

et al. 2015

The American Journal of Pathology

143

121

View full text Add to dashboard Cite

Endometriosis occurs in approximately 10% of women and is associated with persistent pelvic pain. It is defined by the presence of endometrial tissue (lesions) outside the uterus, most commonly on the peritoneum. Peripheral neuroinflammation, a process characterized by the infiltration of nerve fibers and macrophages into lesions, plays a pivotal role in endometriosis-associated pain. Our objective was to determine the role of estradiol (E2) in regulating the interaction between macrophages and nerves in peritoneal endometriosis. By using human tissues and a mouse model of endometriosis, we demonstrate that macrophages in lesions recovered from women and mice are immunopositive for estrogen receptor b, with up to 20% being estrogen receptor a positive. In mice, treatment with E2 increased the number of macrophages in lesions as well as concentrations of mRNAs encoded by Csf1, Nt3, and the tyrosine kinase neurotrophin receptor, TrkB. By using in vitro models, we determined that the treatment of rat dorsal root ganglia neurons with E2 increased mRNA concentrations of the chemokine C-C motif ligand 2 that stimulated migration of colony-stimulating factor 1edifferentiated macrophages. Conversely, incubation of colony-stimulating factor 1 macrophages with E2 increased concentrations of brainderived neurotrophic factor and neurotrophin 3, which stimulated neurite outgrowth from ganglia explants. In summary, we demonstrate a key role for E2 in stimulating macrophage-nerve interactions, providing novel evidence that endometriosis is an estrogen-dependent neuroinflammatory disorder. Endometriosis affects 10% of reproductive age women and is associated with persistent pelvic pain. 1 It is defined by the presence of endometrial-like tissue (lesions) found outside the uterus, most commonly on the peritoneum. The mechanisms underlying endometriosis-associated pain are poorly understood, but it has been postulated that estrogen-dependent neuroinflammation may be involved. 2 Notably, the presence of endometrial tissue fragments on the peritoneum elicits an immune response, including recruitment of macrophages, 3 blood vessels, and nerve fibers into the resultant lesions. 4,5 Within the lesions, CD68 þ macrophages have been detected in close association with nerve fibers. 6 Studies investigating macrophage activation and recruitment have revealed that endometriosis-associated macrophages exhibit a phenotype consistent with the alternative end of the macrophage activation spectrum. 7,8 In a mouse model of endometriosis that included cell transfer of polarized macrophages, Bacci et al 7 reported that mice injected with proinflammatory macrophages [macrophage (interferon g)] developed microscopic lesions, but those injected with alternatively activated macrophages [macrophage (IL-4)] developed larger lesions with a well-developed vasculature. Our studies in a mouse model of endometriosis have revealed that macrophages resident in peritoneal lesions can originate from both the peritoneum and the endometrium. 9

show abstract

“…Although early engagement of macrophages and their consequent state of activation play critical roles in determining the fate of the healing process (23,55,65), the underlying mechanism whereby short-lived fractalkine treatment provides a sustained increase in reparative macrophages and subsequently dramatically better healing remains unclear. Additionally, the particular role of fractalkine and its receptor in the accumulation of monocytes and macrophages at injured peripheral nerves has not been elucidated.…”

Section: Discussionmentioning

confidence: 99%

Immunoengineering nerve repair

Mokarram

Dymanus

Srinivasan

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Injuries to the peripheral nervous system are major sources of disability and often result in painful neuropathies or the impairment of muscle movement and/or normal sensations. For gaps smaller than 10 mm in rodents, nearly normal functional recovery can be achieved; for longer gaps, however, there are challenges that have remained insurmountable. The current clinical gold standard used to bridge long, nonhealing nerve gaps, the autologous nerve graft (autograft), has several drawbacks. Despite best efforts, engineering an alternative "nerve bridge" for peripheral nerve repair remains elusive; hence, there is a compelling need to design new approaches that match or exceed the performance of autografts across critically sized nerve gaps. Here an immunomodulatory approach to stimulating nerve repair in a nerve-guidance scaffold was used to explore the regenerative effect of reparative monocyte recruitment. Early modulation of the immune environment at the injury site via fractalkine delivery resulted in a dramatic increase in regeneration as evident from histological and electrophysiological analyses. This study suggests that biasing the infiltrating inflammatory/immune cellular milieu after injury toward a proregenerative population creates a permissive environment for repair. This approach is a shift from the current modes of clinical and laboratory methods for nerve repair, which potentially opens an alternative paradigm to stimulate endogenous peripheral nerve repair.immunomodulation | nerve repair | monocyte | macrophage | fractalkine P eripheral nervous system (PNS) injuries lead to long-term disability and decreased function in ∼2.8% of all trauma patients (1), and are often followed by neuropathic pain that significantly affects the quality of life for individuals suffering from these injuries. Many of the current surgical techniques for repairing these nerve injuries were developed during World Wars I and II in the first half of the 20th century. With

show abstract

Acute injury in the peripheral nervous system triggers an alternative macrophage response

Cited by 138 publications

References 90 publications

Neutrophils Are Critical for Myelin Removal in a Peripheral Nerve Injury Model of Wallerian Degeneration

Neutrophils Are Critical for Myelin Removal in a Peripheral Nerve Injury Model of Wallerian Degeneration

Estradiol Is a Critical Mediator of Macrophage-Nerve Cross Talk in Peritoneal Endometriosis

Immunoengineering nerve repair

Contact Info

Product

Resources

About