TY - JOUR
T1 - CD36, a class B scavenger receptor, is expressed on microglia in Alzheimer's disease brains and can mediate production of reactive oxygen species in response to β-amyloid fibrils
AU - Coraci, Indra Sethy
AU - Husemann, Jens
AU - Berman, Joan W.
AU - Hulette, Christine
AU - Dufour, Jennifer H.
AU - Campanella, Gabriele K.
AU - Luster, Andrew D.
AU - Silverstein, Samuel C.
AU - El Khoury, Joseph B.
PY - 2002
Y1 - 2002
N2 - A pathological hallmark of Alzheimer's disease is the senile plaque, composed of β-amyloid fibrils, microglia, astrocytes, and dystrophic neurites. We reported previously that class A scavenger receptors mediate adhesion of microglia and macrophages to β-amyloid fibrils and oxidized low-density lipoprotein (oxLDL)-coated surfaces. We also showed that CD36, a class B scavenger receptor and an oxLDL receptor, promotes H2O2 secretion by macrophages adherent to oxLDL-coated surfaces. Whether CD36 is expressed on microglia, and whether it plays a role in secretion of H2O2 by microglia interacting with fibrillar β-amyloid is not known. Using fluorescence-activated cell sorting analysis and immunohistochemistry, we found that CD36 is expressed on human fetal microglia, and N9-immortalized mouse microglia. We also found that CD36 is expressed on microglia and on vascular endothelial cells in the brains of Alzheimer's disease patients. Bowes human melanoma cells, which normally do not express CD36, gained the ability to specifically bind to surfaces coated with fibrillar β-amyloid when transfected with a cDNA encoding human CD36, suggesting that CD36 is a receptor for fibrillar β-amyloid. Furthermore, two different monoclonal antibodies to CD36 inhibited H202 production by N9 microglia and human macrophages adherent to fibrillar β-amyloid by ∼50%. Our data identify a role for CD36 in fibrillar β-amyloid-induced H2O2 production by microglia, and imply that CD36 can mediate binding to fibrillar β-amyloid. We propose that similar to their role in the interaction of macrophages with oxLDL, class A scavenger receptors and CD36 play complimentary roles in the interactions of microglia with fibrillar β-amyloid.
AB - A pathological hallmark of Alzheimer's disease is the senile plaque, composed of β-amyloid fibrils, microglia, astrocytes, and dystrophic neurites. We reported previously that class A scavenger receptors mediate adhesion of microglia and macrophages to β-amyloid fibrils and oxidized low-density lipoprotein (oxLDL)-coated surfaces. We also showed that CD36, a class B scavenger receptor and an oxLDL receptor, promotes H2O2 secretion by macrophages adherent to oxLDL-coated surfaces. Whether CD36 is expressed on microglia, and whether it plays a role in secretion of H2O2 by microglia interacting with fibrillar β-amyloid is not known. Using fluorescence-activated cell sorting analysis and immunohistochemistry, we found that CD36 is expressed on human fetal microglia, and N9-immortalized mouse microglia. We also found that CD36 is expressed on microglia and on vascular endothelial cells in the brains of Alzheimer's disease patients. Bowes human melanoma cells, which normally do not express CD36, gained the ability to specifically bind to surfaces coated with fibrillar β-amyloid when transfected with a cDNA encoding human CD36, suggesting that CD36 is a receptor for fibrillar β-amyloid. Furthermore, two different monoclonal antibodies to CD36 inhibited H202 production by N9 microglia and human macrophages adherent to fibrillar β-amyloid by ∼50%. Our data identify a role for CD36 in fibrillar β-amyloid-induced H2O2 production by microglia, and imply that CD36 can mediate binding to fibrillar β-amyloid. We propose that similar to their role in the interaction of macrophages with oxLDL, class A scavenger receptors and CD36 play complimentary roles in the interactions of microglia with fibrillar β-amyloid.
UR - http://www.scopus.com/inward/record.url?scp=0036141148&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036141148&partnerID=8YFLogxK
U2 - 10.1016/S0002-9440(10)64354-4
DO - 10.1016/S0002-9440(10)64354-4
M3 - Article
C2 - 11786404
AN - SCOPUS:0036141148
SN - 0002-9440
VL - 160
SP - 101
EP - 112
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 1
ER -