Polymorphonuclear leukocytes promote neurotoxicity through release of matrix metalloproteinases, reactive oxygen species, and TNF-α

Nguyen, Hal X.; O'Barr, Thaddeus J.; Anderson, Aileen J.

doi:10.1111/j.1471-4159.2007.004643.x

Cited by 139 publications

(32 citation statements)

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“…In line with our recent observations in BoyJ mice subjected to pMCAo (Clausen et al, 2008), we also in the present study found that TNF-producing microglia outnumbered the TNF-synthesizing macrophages at 24 h, thereby also strengthening our in situ hybridization results suggestive that microglia are the first and possibly the only resident CNS cell induced to express TNF mRNA in the ischemic brain. Importantly, we failed to observe synthesis of TNF by Gr-1 ϩ granulocytes and TCR␤ ϩ T-cells 24 h after pMCAo, although reports by others have indicated that these cell types may produce TNF, at least in vitro (Lafont et al, 2000;Nguyen et al, 2007).…”

Section: Discussionmentioning

confidence: 45%

Microglia Protect Neurons against Ischemia by Synthesis of Tumor Necrosis Factor

Lambertsen¹,

Clausen²,

Babcock³

et al. 2009

J. Neurosci.

334

352

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Microglia and infiltrating leukocytes are considered major producers of tumor necrosis factor (TNF), which is a crucial player in cerebral ischemia and brain inflammation. We have identified a neuroprotective role for microglial-derived TNF in cerebral ischemia in mice. We show that cortical infarction and behavioral deficit are significantly exacerbated in TNF-knock-out (KO) mice compared with wild-type mice. By using in situ hybridization, immunohistochemistry, and green fluorescent protein bone marrow (BM)-chimeric mice, TNF was shown to be produced by microglia and infiltrating leukocytes. Additional analysis demonstrating that BM-chimeric TNF-KO mice grafted with wild-type BM cells developed larger infarcts than BM-chimeric wild-type mice grafted with TNF-KO BM cells provided evidence that the neuroprotective effect of TNF was attributable to microglial-not leukocyte-derived TNF. In addition, observation of increased infarction in TNF-p55 receptor (TNF-p55R)-KO mice compared with TNF-p75R and wild-type mice suggested that microglialderived TNF exerts neuroprotective effects through TNF-p55R. We finally report that TNF deficiency is associated with reduced microglial population size and Toll-like receptor 2 expression in unmanipulated brain, which might also influence the neuronal response to injury. Our results identify microglia and microglial-derived TNF as playing a key role in determining the survival of endangered neurons in cerebral ischemia.

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Section: Discussionmentioning

confidence: 45%

Microglia Protect Neurons against Ischemia by Synthesis of Tumor Necrosis Factor

Lambertsen¹,

Clausen²,

Babcock³

et al. 2009

J. Neurosci.

334

352

View full text Add to dashboard Cite

show abstract

“…Whilst there is considerable evidence that neutrophils contribute to inflammatory injury in rodent models of neuronal injury (Ryu et al, 2007;Taoka et al, 1997;Yamasaki et al, 1997), neutrophil invasion of dorsal root ganglia (DRG) occurs rarely (McLachlan et al, 2007;Morin et al, 2007). Neutrophils can, however, promote neurotoxicity of DRG in vitro by release of metalloproteinases, reactive oxygen species and cytokines (Nguyen et al, 2007;Shaw et al, 2008), suggesting that regulatory mechanisms may limit infiltration of neutrophils into ganglia during acute HSV-1 infection to avoid immunopathological destruction of sensory neurons. Previous studies have described early infiltration of NK cells and cd-TCR + cells, and subsequently CD8…”

Section: Discussionmentioning

confidence: 99%

Depletion of Gr-1+, but not Ly6G+, immune cells exacerbates virus replication and disease in an intranasal model of herpes simplex virus type 1 infection

Wojtasiak

Pickett

Tate

et al. 2010

Journal of General Virology

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“…PMN and Mf synthesize multiple cytokines and chemokines, including TNF-a (24,45,46). As well, we and others have shown that some components of the complement cascade, specifically C1q and C3, are synthesized by PMN and Mf both in vitro and in vivo following neurodegeneration (47)(48)(49).…”

Section: Pmn-and Mf-cm Factorsmentioning

confidence: 99%

“…and were sacrificed 12-16 h later (to obtain PMN) or 3-5 d later (to obtain Mf), as described previously (24). The peritoneal exudate containing leukocytes was overlaid on Histopaque 1077 (Sigma-Aldrich) and centrifuged at 400 3 g to separate PMN (12-16 h postsodium caseinate) or Mf (3-5 d postsodium caseinate) from other leukocytes, yielding 97% PMN and 80% F4/80 + Mf, respectively.…”

Section: Generation Of Pmn or Mf-cmmentioning

confidence: 99%

Neutrophils Induce Astroglial Differentiation and Migration of Human Neural Stem Cells via C1q and C3a Synthesis

Hooshmand

Nguyen

Piltti

et al. 2017

The Journal of Immunology

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Inflammatory processes play a key role in pathophysiology of many neurologic diseases/trauma, but the effect of immune cells and factors on neurotransplantation strategies remains unclear. We hypothesized that cellular and humoral components of innate immunity alter fate and migration of human neural stem cells (hNSC). In these experiments, conditioned media collected from polymorphonuclear leukocytes (PMN) selectively increased hNSC astrogliogenesis and promoted cell migration in vitro. PMN were shown to generate C1q and C3a; exposure of hNSC to PMN-synthesized concentrations of these complement proteins promoted astrogliogenesis and cell migration. Furthermore, in vitro, Abs directed against C1q and C3a reversed the fate and migration effects observed. In a proof-of-concept in vivo experiment, blockade of C1q and C3a transiently altered hNSC migration and reversed astroglial fate after spinal cord injury. Collectively, these data suggest that modulation of the innate/humoral inflammatory microenvironment may impact the potential of cell-based therapies for recovery and repair following CNS pathology.

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Polymorphonuclear leukocytes promote neurotoxicity through release of matrix metalloproteinases, reactive oxygen species, and TNF-α

Cited by 139 publications

References 0 publications

Microglia Protect Neurons against Ischemia by Synthesis of Tumor Necrosis Factor

Microglia Protect Neurons against Ischemia by Synthesis of Tumor Necrosis Factor

Depletion of Gr-1+, but not Ly6G+, immune cells exacerbates virus replication and disease in an intranasal model of herpes simplex virus type 1 infection

Neutrophils Induce Astroglial Differentiation and Migration of Human Neural Stem Cells via C1q and C3a Synthesis

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