Balancing function vs. self defense: The CNS as an active regulator of immune responses

Sutcliffe, J. Gregor

doi:10.1002/(sici)1097-4547(19990101)55:1<1::aid-jnr1>3.0.co;2-9

Cited by 92 publications

(41 citation statements)

References 66 publications

(75 reference statements)

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“…Microglia regulate the initiation and progression of immune responses in the CNS (reviewed in Carson & Sutcliffe, 1999). Primary cultures of rat and mouse microglia express both CB 1 and CB 2 receptor mRNA and protein (Sinha et al, 1998;Carlisle et al, 2002;Facchinetti et al, 2003;Walter et al, 2003a).…”

Section: Glial Cells Express Cannabinoid Receptorsmentioning

confidence: 99%

“…Peripheral immune cells also participate in the neuroinflammatory response (reviewed in Carson & Sutcliffe, 1999). CB 2 receptor mRNA is expressed, in decreasing rank order, by human B cells, NK cells, monocytes, neutrophils, and T cells at levels 10 to 100 times higher than CB 1 receptor mRNA (Galiegue et al, 1995).…”

Section: Peripheral Immune Cells Express Cannabinoid Receptorsmentioning

confidence: 99%

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Cannabinoids and neuroinflammation

Walter

Stella

2004

British J Pharmacology

306

215

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Growing evidence suggests that a major physiological function of the cannabinoid signaling system is to modulate neuroinflammation. This review discusses the anti-inflammatory properties of cannabinoid compounds at molecular, cellular and whole animal levels, first by examining the evidence for anti-inflammatory effects of cannabinoids obtained using in vivo animal models of clinical neuroinflammatory conditions, specifically rodent models of multiple sclerosis, and second by describing the endogenous cannabinoid (endocannabinoid) system components in immune cells. Our aim is to identify immune functions modulated by cannabinoids that could account for their antiinflammatory effects in these animal models.

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Section: Glial Cells Express Cannabinoid Receptorsmentioning

confidence: 99%

Section: Peripheral Immune Cells Express Cannabinoid Receptorsmentioning

confidence: 99%

Cannabinoids and neuroinflammation

Walter

Stella

2004

British J Pharmacology

306

215

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“…Microglia are derived from circulating monocytes and function as resident immune cells of the CNS (Kreutzberg, 1996;Carson and Sutcliffe, 1999). Resting microglia have branched processes and maintain regular spacing throughout the brain and spinal cord.…”

Section: Introductionmentioning

confidence: 99%

Zinc Triggers Microglial Activation

Kauppinen

Higashi²,

Suh³

et al. 2008

J. Neurosci.

160

172

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Microglia are resident immune cells of the CNS. When stimulated by infection, tissue injury, or other signals, microglia assume an activated, "ameboid" morphology and release matrix metalloproteinases, reactive oxygen species, and other proinflammatory factors. This innate immune response augments host defenses, but it can also contribute to neuronal death. Zinc is released by neurons under several conditions in which microglial activation occurs, and zinc chelators can reduce neuronal death in animal models of cerebral ischemia and neurodegenerative disorders. Here, we show that zinc directly triggers microglial activation. Microglia transfected with a nuclear factor-B (NF-B) reporter gene showed a severalfold increase in NF-B activity in response to 30 M zinc. Cultured mouse microglia exposed to 15-30 M zinc increased nitric oxide production, increased F4/80 expression, altered cytokine expression, and assumed the activated morphology. Zinc-induced microglial activation was blocked by inhibiting NADPH oxidase, poly(ADP-ribose) polymerase-1 (PARP-1), or NF-B activation. Zinc injected directly into mouse brain induced microglial activation in wild-type mice, but not in mice genetically lacking PARP-1 or NADPH oxidase activity. Endogenous zinc release, induced by cerebral ischemia-reperfusion, likewise induced a robust microglial reaction, and this reaction was suppressed by the zinc chelator CaEDTA. Together, these results suggest that extracellular zinc triggers microglial activation through the sequential activation of NADPH oxidase, PARP-1, and NF-B. These findings identify a novel trigger for microglial activation and a previously unrecognized mechanism by which zinc may contribute to neurological disorders.

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“…Close interaction of the central nervous system (CNS) and immune cells has become more evident in recent years. Immune cell function is modulated by neuroendocrines as well as by neurotransmitters and vice versa (Hanisch et al, 1996;Carson and Sutcliffe, 1999). In addition, neurodegenerative diseases, such as dementia of Alzheimer type (DAT (Eckert et al, 1998(Eckert et al, , 2001Schindowski et al, 1999)), Down's Syndrome (DS (Park et al, 2000)) and the demyelating disease, multiple sclerosis (MS (Crucian et al, 1995a)) are accompanied by altered lymphocyte function and apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Age-related impairment of human T lymphocytes’ activation: specific differences between CD4+ and CD8+ subsets

Schindowski

Fröhlich

Maurer

et al. 2002

Mechanisms of Ageing and Development

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The relevance of physiological immune aging is of great interest with respect to determining disorders with pathologic immune function in aging individuals. In recent years, the relevance of changes in peripheral lymphocytes in age-associated neurologic diseases has become more evident. Due to the lack of immunological studies. covering moce than one event after mitogenic activation, we envisaged a new concept in the present study, aiming to investigate several events, starting from T cell receptor (TCR) ligation up to T cell proliferation. In addition, we addressed the question whether changes are present in the subsets (CD4, CDR) with aging. Phosphorylation of tyrosine residues declines with increasing age in CD4+ cells. Fewer levels of CD69 positive cells after 4 h mitogenic activation, altered expression of cytokines (IL2, IFN-7 and TNF-a; 22 h) and lower proliferation (72 h) were detemined in aging. Moreover, it could be shown that CD8" lymphocytes react more effectively to mitogenic stirnulation with referenoe to CD69 expression and proliferation in both age groups ( < 35 and > 60 years old). These data indicate that T cell activation, rnediated by TCR engagement, is significantly impaired in aging and both subsets are affected. However, bypassing the TCR does not fully restore T cell function, indicating that there are more mechanisms involved than impaired signal transduction thwugh TCR only. The results will be discussed in relation to iiheir relevance in neurodegenerative and psychiatric disorders.

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Balancing function vs. self defense: The CNS as an active regulator of immune responses

Cited by 92 publications

References 66 publications

Cannabinoids and neuroinflammation

Cannabinoids and neuroinflammation

Zinc Triggers Microglial Activation

Age-related impairment of human T lymphocytes’ activation: specific differences between CD4+ and CD8+ subsets

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