Scavenger Receptors Class A-I/II and CD36 Are the Principal Receptors Responsible for the Uptake of Modified Low Density Lipoprotein Leading to Lipid Loading in Macrophages*

By V. Kunjathoor, M. Febbraio, E. Podrez, K. Moore, L. Andersson, Stephanie L Koehn, J. S. Rhee, R. Silverstein, H. Hoff, M. Freeman. Journal of Biological Chemistry, 2002

1,046 citations recorded by the source corpus.

Modification of low density lipoprotein (LDL) can result in the avid uptake of these lipoproteins via a family of macrophage transmembrane proteins referred to as scavenger receptors (SRs). The genetic inactivation of either of two SR family members, SR-A or CD36, has been shown previously to reduce oxidized LDL uptakein vitro and atherosclerotic lesions in mice. Several other SRs are reported to bind modified LDL, but their contribution to macrophage lipid accumulation is uncertain. We generated mice lacking both SR-A and CD36 to determine their combined impact on macrophage lipid uptake and to assess the contribution of other SRs to this process. We show that SR-A and CD36 account for 75–90% of degradation of LDL modified by acetylation or oxidation. Cholesteryl ester derived from modified lipoproteins fails to accumulate in macrophages taken from the double null mice, as assessed by histochemistry and gas chromatography-mass spectrometry. These results demonstrate that SR-A and CD36 are responsible for the preponderance of modified LDL uptake in macrophages and that other scavenger receptors do not compensate for their absence.

Subfields: Cancer Research, Molecular Biology, Surgery

View Paper: https://www.semanticscholar.org/paper/f7db28c8e3c732dd65efa5eba2be6d6edc9f6ae4

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. D. Golenbock
2. Katherine A. Fitzgerald
3. Shizuo Akira

In Molecular Biology

1. E. Latz
2. Katherine A. Fitzgerald
3. K. Moore
4. A. Grebe
5. Florian Hoss
6. J. Tschopp
7. T. Kanneganti

In Surgery

1. K. Moore

Citations in the corpus

• The Cellular Biology of Macrophages in Atherosclerosis (2011, neutral): “Importantly, atherosclerotic mousemodels lacking two SRs, SRA andCD36, or two TLRs, TLR4 and TLR2, are partially protected against advanced lesional macrophage death and plaque necrosis in a manner that cannot be explained simply by other effects on early plaque progression.”
• Oxidized Low-Density Lipoprotein Induces Long-Term Proinflammatory Cytokine Production and Foam Cell Formation via Epigenetic Reprogramming of Monocytes (2014, background): “Trained Monocytes Have an Increased Expression of Scavenger Receptors and Reduced Expression of Cholesterol Efflux Transporters OxLDL is taken up by macrophages via scavenger receptors, of which CD36 and SR-A are considered the most important.(5) Interestingly, the genes of these receptors showed en”
• NLRP3 Inflammasome and the IL-1 Pathway in Atherosclerosis. (2018, background): “ceptors, such as CD (cluster of differentiation) 36, mediate the uptake of oxLDL into macrophages.(176) Moreover, oxLDL”
• CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer (2009, background): “We therefore tested whether fibrillar β-amyloid peptide (1-42) (Aβ1-42) could activate TLR4-TLR6 signaling via CD36.”
• CD36 coordinates NLRP3 inflammasome activation by facilitating the intracellular nucleation from soluble to particulate ligands in sterile inflammation (2013, background): “In the AD brain and diabetic pancreas, amyloid plaques arise from the aggregation of pre-fibrillar amyloidogenic peptides such as the Aβ(1-42) peptide17, 18, 19 or IAPP20, 21, 22, which oligomerize and give rise to higher order structures, including fibrils.”