Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH MEDIA
GLOBETECH PUBLISHING LLC
GLOBETECH PUBLISHING LLC

Blocking Action of a Macrophage Surface Protein Limits Damage in Chronic Inflammatory Diseases

By BiotechDaily International staff writers
Posted on 18 Jul 2013
Image: Predicted topology of CD36 in the plasma membrane (Photo courtesy of Wikimedia Commons).
Image: Predicted topology of CD36 in the plasma membrane (Photo courtesy of Wikimedia Commons).
The macrophage integral membrane protein CD36 (Cluster of Differentiation 36) has been identified as a central regulator of inflammasome activation in several chronic inflammatory disease such as atherosclerosis, Alzheimer's disease, and diabetes.

The inflammasome is a multiprotein oligomer consisting of caspase 1, PYCARD, NALP, and sometimes caspase 5. It is expressed in myeloid cells and is a component of the innate immune system. The exact composition of an inflammasome depends on the activator that initiates its assembly. For example, dsRNA will trigger one inflammasome composition while asbestos will assemble a different variant. An inflammasome promotes the maturation of inflammatory cytokines interleukin 1-beta (IL-1-beta) and interleukin 18 (IL-18). The inflammasome is responsible for activation of inflammatory processes and has been shown to induce cell pyroptosis, a process of programmed cell death distinct from apoptosis.

CD36 is a member of the class B scavenger receptor family of cell surface proteins. As such, it binds many ligands including collagen, thrombospondin, erythrocytes infected with the malaria parasite Plasmodium falciparum, oxidized low-density lipoprotein (LDL), native lipoproteins, oxidized phospholipids, and long-chain fatty acids. It was thought that CD36 mediated removal of particulate inflammatory ligands such as amyloid plaques or cholesterol crystals.

A paper published in the June 30, 2013, online edition of the journal Nature Immunology better defined the role of CD36 in the inflammatory process. Investigators at the New York University Langone Medical Center (NY, USA) reported that CD36 coordinated the immune response to soluble endogenous ligands, including oxidized LDL, and amyloid-beta and amylin peptides that accumulate in various chronic inflammatory diseases. They identified an endocytic pathway mediated by the pattern-recognition receptor conversion of those soluble ligands into crystals or fibrils, which resulted in lysosomal disruption and activation of the NLRP3 inflammasome. Consequently, macrophages that lacked CD36 failed to elicit IL-1-beta production in response to those ligands, and targeting CD36 in atherosclerotic mice resulted in lower serum concentrations of IL-1-beta and accumulation of fewer cholesterol crystals into atherosclerotic plaques.

“Our findings identify CD36 as a central regulator of the immune response in these conditions and suggest that blocking CD36 might be a common therapeutic option for all three diseases,” said senior author Dr. Kathryn J. Moore, associate professor of medicine and cell biology, at the New York University Langone Medical Center.

“What we found is that CD36 binds soluble cholesterol and protein matter associated with these diseases, pulls them inside the cell, and then transforms them. The resulting insoluble crystals and amyloid damage the macrophage and trigger a powerful cytokine, called interleukin-1-beta, linked to a chronic inflammatory response.”

Related Links:
New York University Langone Medical Center


Channels

Drug Discovery

view channel
Image: Molecular model of the protein Saposin C (Photo courtesy of Wikimedia Commons).

Nanovesicles Kill Human Lung Cancer Cells in Culture and in a Mouse Xenograft Model

Nanovesicles assembled from the protein Saposin C (SapC) and the phospholipid dioleoylphosphatidylserine (DOPS) were shown to be potent inhibitors of lung cancer cells in culture and in a mouse xenograft model.... Read more

Biochemistry

view channel

Possible New Target Found for Treating Brain Inflammation

Scientists have identified an enzyme that produces a class of inflammatory lipid molecules in the brain. Abnormally high levels of these molecules appear to cause a rare inherited eurodegenerative disorder, and that disorder now may be treatable if researchers can develop suitable drug candidates that suppress this enzyme.... Read more

Lab Technologies

view channel
Image: The FLUOVIEW FVMPE-RS Gantry microscope (Photo courtesy of Olympus).

New Multiphoton Laser Scanning Microscope Configurations Expand Research Potential

Two new configurations of a state-of-the-art multiphoton laser scanning microscope extend the usefulness of the instrument for examining rapidly occurring biological events and for obtaining images from... Read more

Business

view channel

Roche Acquires Signature Diagnostics to Advance Translational Research

Roche (Basel, Switzerland) will advance translational research for next generation sequencing (NGS) diagnostics by leveraging the unique expertise of Signature Diagnostics AG (Potsdam, Germany) in biobanks and development of novel NGS diagnostic assays. Signature Diagnostics is a privately held translational oncology... Read more
 
Copyright © 2000-2015 Globetech Media. All rights reserved.