Immunoadjuvanticity of Endotoxins and Nontoxic Derivatives for Normal and Leukemic Immunocytes

The effects of an ornithine-containing lipid [ot-N-(3-acyloxyacyl)-ornithine (Orn-L)] or a serine-containing lipid [a-N-(3-acyloxyacyl)-serine (Ser-L)] from Flavobacterium meningosepticum on lethal endotoxemia in mice were examined. When 500 ,ug of Orn-L was intravenously administered 1 h before intravenous administration of a lethal dose of endotoxin, none of the mice died. The protective effect of Ser-L was weaker than that of Orn-L. Light and electron microscopic studies demonstrated that necrosis of hepatocytes caused by endotoxin was prevented by pretreatment with Orn-L. Furthermore, Kupffer cells were activated morphologically 1 h after the administration of Orn-L or Ser-L, and the liposomes of the lipoamino acids were incorporated into phagolysosomes in activated Kupffer cells. The activity of tumor necrosis factor in sera of endotoxin-treated mice was decreased markedly by pretreatment of mice with Orn-L. In vitro, the lipoamino acids suppressed endotoxin-induced tumor necrosis factor generation but did not suppress tumor necrosis factor generation induced by zymosan and whole cells of Staphylococcus aureus. These results suggested that Orn-L and Ser-L can be used as specific blocking agents against endotoxin. The blocking mechanism may be antagonistic, because of the structural similarities between the lipoamino acids and endotoxin lipid A.

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“…These results have been reported previously (9). On the other hand, endotoxin is known also to exhibit all of these activities (4,18,19).…”

supporting

confidence: 89%

“…Arrowheads show dense materials, and asterisks show lipid droplets. 4. Time course of TNF activity in sera.…”

Section: Asmentioning

confidence: 99%

Protection of mice from lethal endotoxemia by use of an ornithine-containing lipid or a serine-containing lipid

et al. 1991

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“…Astrocytes respond to chronic CNS injuries and diseases by differentiating and proliferating into hypertrophic and/or migrating cell types-a term referred to as reactive astrocytosis (Khakh and Sofroniew, 2015;Liddelow and Barres, 2015;Sofroniew and Vinters, 2010). Reactive astrocytosis may have both reparative functions that preserve synaptic homeostasis (eg, increasing the secretion of neurotrophic factors such as nerve growth factor, brain-derived neurotrophic factor [BDNF], and activity-dependent neurotrophic growth factor, and increasing glutamate clearance through cradling and reuptake mechanisms) or toxic functions resulting in neuronal loss (Friedman et al, 1990;Liberto et al, 2004;Marz et al, 1999;Spranger et al, 1990). Accordingly, reactive astrocytes can be classified into A1 and A2 astrocytes (Karpuk et al, 2012).…”

Section: Immune Regulationmentioning

confidence: 99%

Inflammation, Glutamate, and Glia: A Trio of Trouble in Mood Disorders

Haroon

Miller

Sanacora

2016

Neuropsychopharmacol

383

299

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Increasing data indicate that inflammation and alterations in glutamate neurotransmission are two novel pathways to pathophysiology in mood disorders. The primary goal of this review is to illustrate how these two pathways may converge at the level of the glia to contribute to neuropsychiatric disease. We propose that a combination of failed clearance and exaggerated release of glutamate by glial cells during immune activation leads to glutamate increases and promotes aberrant extrasynaptic signaling through ionotropic and metabotropic glutamate receptors, ultimately resulting in synaptic dysfunction and loss. Furthermore, glutamate diffusion outside the synapse can lead to the loss of synaptic fidelity and specificity of neurotransmission, contributing to circuit dysfunction and behavioral pathology. This review examines the fundamental role of glia in the regulation of glutamate, followed by a description of the impact of inflammation on glial glutamate regulation at the cellular, molecular, and metabolic level. In addition, the role of these effects of inflammation on glia and glutamate in mood disorders will be discussed along with their translational implications.

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Fever, Pyrogens and Cancer

Kleef¹,

Hager

Medical Intelligence Unit

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Immunoadjuvanticity of Endotoxins and Nontoxic Derivatives for Normal and Leukemic Immunocytes

Cited by 4 publications

References 7 publications

Protection of mice from lethal endotoxemia by use of an ornithine-containing lipid or a serine-containing lipid

Protection of mice from lethal endotoxemia by use of an ornithine-containing lipid or a serine-containing lipid

Inflammation, Glutamate, and Glia: A Trio of Trouble in Mood Disorders

Fever, Pyrogens and Cancer

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