MAC1 mediates LPS-induced production of superoxide by microglia: the role of pattern recognition receptors in dopaminergic neurotoxicity.

MAC1 mediates LPS-induced production of superoxide by microglia: the role of pattern recognition receptors in dopaminergic neurotoxicity. Research Abstract Details 

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MAC1 mediates LPS-induced production of superoxide by microglia: the role of pattern recognition receptors in dopaminergic neurotoxicity. Abstract Text:

Zhong Pei,Hao Pang,Li Qian,Sufen Yang,Tonggauang Wang,Wei Zhang,Xeufei Wu,Shannon Dallas,Belinda Wilson,Jeffrey M Reece,David S Miller,Jau-Shyong Hong,Michelle L Block,

Microglia-derived superoxide is critical for the inflammation-induced selective loss of dopaminergic (DA) neurons, but the underlying mechanisms of microglial activation remain poorly defined. Using neuron-glia and microglia-enriched cultures from mice deficient in the MAC1 receptor (MAC1-/-), we demonstrate that lipopolysaccharide (LPS) treatment results in lower TNFalpha response, attenuated loss of DA neurons, and absence of extracellular superoxide production in MAC1-/- cultures. Microglia accumulated fluorescently labeled LPS in punctate compartments associated with the plasma membrane, intracellular vesicles, and the Golgi apparatus. Cytochalasin D (CD), an inhibitor of phagocytosis, blocked LPS internalization. However, microglia derived from Toll-like receptor 4 deficient mice and MAC1-/- mice failed to show a significant decrease in intracellular accumulation of labeled LPS, when compared with controls. Pretreatment with the scavenger receptor inhibitor, fucoidan, inhibited 79% of LPS accumulation in microglia without affecting superoxide, indicating that LPS internalization and superoxide production are mediated by separate phagocytosis receptors. Together, these data demonstrate that MAC1 is essential for LPS-induced superoxide from microglia, implicating MAC1 as a critical trigger of microglial-derived oxidative stress during inflammation-mediated neurodegeneration.

MAC1 mediates LPS-induced production of superoxide by microglia: the role of pattern recognition receptors in dopaminergic neurotoxicity. Publishing Authors By Initials

Z Pei,H Pang,L Qian,S Yang,T Wang,W Zhang,X Wu,S Dallas,B Wilson,JM Reece,DS Miller,JS Hong,ML Block,

For similar proteins: membrane proteins: receptors, cell surface: receptors, immunologic: receptors, pattern recognition: toll-like receptors: toll-like receptor 4 research abstracts see: proteins: membrane proteins: receptors, cell surface: receptors, immunologic: receptors, pattern recognition: toll-like receptors: toll-like receptor 4 research

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MAC1 mediates LPS-induced production of superoxide by microglia: the role of pattern recognition receptors in dopaminergic neurotoxicity. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Glia

VOLUME: 55

Page Numbers: 1362-73

Journal Abbreviation: Glia

ISSN: 0894-1491

DAY: 3

MONTH: Oct

YEAR: 2007

MAC1 mediates LPS-induced production of superoxide by microglia: the role of pattern recognition receptors in dopaminergic neurotoxicity. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8806785

MAC1 mediates LPS-induced production of superoxide by microglia: the role of pattern recognition receptors in dopaminergic neurotoxicity. Keywords Mesh Terms:

KEYWORDS: Toll-Like Receptor 4

MESH TERMS: metabolism

Chemical & Substance for Abstract: MAC1 mediates LPS-induced production of superoxide by microglia: the role of pattern recognition receptors in dopaminergic neurotoxicity. Information

Substance Name: NADPH Oxidase

Registry Number: EC 1.6.3.1

Grant and Affiliation Information for MAC1 mediates LPS-induced production of superoxide by microglia: the role of pattern recognition receptors in dopaminergic neurotoxicity.

AFFILIATION: Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.

Country: United States

AGENCY: United States NIEHS

GRANT: 1K99ES01549-01

ACRONYM: ES

MEDLINETA: Glia

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