A CD36-initiated Signaling Cascade Mediates Inflammatory Effects of β-Amyloid

Moore, Kathryn J.; Khoury, Joseph El; Medeiros, Lea A.; Terada, Kinya; Geula, Changiz; Luster, Andrew D.; Freeman, Mason W.

doi:10.1074/jbc.m208788200

Cited by 313 publications

(304 citation statements)

References 28 publications

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“…Both Webster et al (2001) and Das et al (2003) demonstrated A␤ phagocytosis in the presence of immune complexes in vitro; however, this result was only observed with the addition of fucoidan, which acted to block scavenger receptor binding. We and others have demonstrated the requirement for the B-class scavenger receptor CD36 participation in fA␤-stimulated microglia activation (Moore et al, 2002;Bamberger et al, 2003;El Khoury et al, 2003). The present study has established that CD36 is also essential for stimulation of fA␤ phagocytosis by microglia.…”

Section: Discussionmentioning

confidence: 48%

Microglial Phagocytosis of Fibrillar β-Amyloid through a β₁Integrin-Dependent Mechanism

Koenigsknecht

Landreth²

2004

J. Neurosci.

400

347

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Microglia are the principle immune effector and phagocytic cells in the CNS. These cells are associated with fibrillar ␤-amyloid (fA␤)-containing plaques found in the brains of Alzheimer's disease (AD) patients. The plaque-associated microglia undergo a phenotypic conversion into an activated phenotype and are responsible for the development of a focal inflammatory response that exacerbates and accelerates the disease process. Paradoxically, despite the presence of abundant activated microglia in the brain of AD patients, these cells fail to mount a phagocytic response to A␤ deposits but can efficiently phagocytose A␤ fibrils and plaques in vitro.We report that exposure of microglia to fA␤ in vitro induces phagocytosis through mechanisms distinct from those used by the classical phagocytic receptors, the Ig receptors (FcR␥I and Fc␥RIII) or complement receptors. Microglia interact with fA␤ through a recently characterized A␤ cell surface receptor complex comprising the B-class scavenger receptor CD36, ␣ 6 ␤ 1 integrin, and CD47 (integrin-associated protein). Antagonists specific for each component of the receptor complex blocks fA␤-stimulated phagocytosis. These data demonstrated that engagement of this ensemble of receptors is required for induction of phagocytosis. The phagocytic response stimulated by this receptor complex is driven principally by a ␤ 1 integrin-linked process that is morphologically and mechanistically distinct from the classical type I and type II phagocytic mechanisms. These data provide evidence for phagocytic uptake of fA␤ through a receptor-mediated, nonclassical phagocytic mechanism.

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Section: Discussionmentioning

confidence: 48%

Microglial Phagocytosis of Fibrillar β-Amyloid through a β₁Integrin-Dependent Mechanism

Koenigsknecht

Landreth²

2004

J. Neurosci.

400

347

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“…The methods for preparing Aβ oligomers or fibrils had been described previously (Dahlgren et al ., 2002; Moore et al ., 2002; Pan et al ., 2011). The detailed information was provided in the supportive information.…”

Section: Methodsmentioning

confidence: 99%

Prostaglandin I ₂ upregulates the expression of anterior pharynx‐defective‐1α and anterior pharynx‐defective‐1β in amyloid precursor protein/presenilin 1 transgenic mice

et al. 2016

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SummaryCyclooxygenase‐2 (COX‐2) has been recently identified to be involved in the pathogenesis of Alzheimer's disease (AD). Yet, the role of an important COX‐2 metabolic product, prostaglandin (PG) I2, in the pathogenesis of AD remains unknown. Using human‐ and mouse‐derived neuronal cells as well as amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice as model systems, we elucidated the mechanism of anterior pharynx‐defective (APH)‐1α and pharynx‐defective‐1β induction. In particular, we found that PGI 2 production increased during the course of AD development. Then, PGI 2 accumulation in neuronal cells activates PKA/CREB and JNK/c‐Jun signaling pathways by phosphorylation, which results in APH‐1α/1β expression. As PGI 2 is an important metabolic by‐product of COX‐2, its suppression by NS398 treatment decreases the expression of APH‐1α/1β in neuronal cells and APP/PS1 mice. More importantly, β‐amyloid protein (Aβ) oligomers in the cerebrospinal fluid (CSF) of APP/PS1 mice are critical for stimulating the expression of APH‐1α/1β, which was blocked by NS398 incubation. Finally, the induction of APH‐1α/1β was confirmed in the brains of patients with AD. Thus, these findings not only provide novel insights into the mechanism of PGI 2‐induced AD progression but also are instrumental for improving clinical therapies to combat AD.

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“…It is pertinent to point out that there would appear to be major differences in the signaling pathways and the initiation of inflammatory responses between different scavenger receptors. For example, deletion of the class B receptor, CD36, diminishes the proinflammatory response of M to ␤-amyloid (26).…”

Section: Discussionmentioning

confidence: 99%

The Class A Macrophage Scavenger Receptor Attenuates CXC Chemokine Production and the Early Infiltration of Neutrophils in Sterile Peritonitis

Cotena

Gordon

Platt

2004

The Journal of Immunology

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The macrophage scavenger receptor (SR-A) is a multifunctional receptor that is associated with several important pathological conditions, including atherosclerosis. In this study, we show, using a sterile peritonitis model, that it can regulate the inflammatory response. SR-A null mice display an increased initial granulocytic infiltration because of overproduction of the CXC chemokines, MIP-2 and keratinocyte-derived cytokine. This differential response is dependent upon particle internalization and can be mimicked by advanced glycation end product-BSA-conjugated latex beads. Thus SR-A is a nonactivating receptor, which is the first example of a pattern recognition receptor that serves to counter the activities of proinflammatory receptors and attenuates the production of specific chemokines to ensure an inflammatory response of the appropriate magnitude.

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A CD36-initiated Signaling Cascade Mediates Inflammatory Effects of β-Amyloid

Cited by 313 publications

References 28 publications

Microglial Phagocytosis of Fibrillar β-Amyloid through a β₁Integrin-Dependent Mechanism

Microglial Phagocytosis of Fibrillar β-Amyloid through a β₁Integrin-Dependent Mechanism

Prostaglandin I ₂ upregulates the expression of anterior pharynx‐defective‐1α and anterior pharynx‐defective‐1β in amyloid precursor protein/presenilin 1 transgenic mice

The Class A Macrophage Scavenger Receptor Attenuates CXC Chemokine Production and the Early Infiltration of Neutrophils in Sterile Peritonitis

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A CD36-initiated Signaling Cascade Mediates Inflammatory Effects of β-Amyloid

Cited by 313 publications

References 28 publications

Microglial Phagocytosis of Fibrillar β-Amyloid through a β1Integrin-Dependent Mechanism

Microglial Phagocytosis of Fibrillar β-Amyloid through a β1Integrin-Dependent Mechanism

Prostaglandin I 2 upregulates the expression of anterior pharynx‐defective‐1α and anterior pharynx‐defective‐1β in amyloid precursor protein/presenilin 1 transgenic mice

The Class A Macrophage Scavenger Receptor Attenuates CXC Chemokine Production and the Early Infiltration of Neutrophils in Sterile Peritonitis

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Microglial Phagocytosis of Fibrillar β-Amyloid through a β₁Integrin-Dependent Mechanism

Microglial Phagocytosis of Fibrillar β-Amyloid through a β₁Integrin-Dependent Mechanism

Prostaglandin I ₂ upregulates the expression of anterior pharynx‐defective‐1α and anterior pharynx‐defective‐1β in amyloid precursor protein/presenilin 1 transgenic mice