Microglial cells internalize aggregates of the Alzheimer's disease amyloid beta-protein via a scavenger receptor

被引:574
作者
Paresce, DM
Ghosh, RN
Maxfield, FR
机构
[1] COLUMBIA UNIV, DEPT BIOL, NEW YORK, NY 10032 USA
[2] COLUMBIA UNIV, ALZHEIMERS DIS RES CTR, NEW YORK, NY 10032 USA
[3] COLUMBIA UNIV, CTR NEUROBIOL & BEHAV, NEW YORK, NY 10032 USA
[4] CORNELL UNIV, COLL MED, DEPT BIOCHEM, NEW YORK, NY 10021 USA
关键词
D O I
10.1016/S0896-6273(00)80187-7
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Microglia are immune system cells associated with Alzheimer's disease plaques containing beta-amyloid (A beta). Murine microglia internalize microaggregates of fluorescently labeled or radioiodinated A beta peptide 1-42. Uptake was confirmed using aggregates of unlabeled A beta detected by immunofluorescence. Uptake of A beta was reduced by coincubation with excess acetyl-low density lipoprotein (Ac-LDL) or other scavenger receptor (SR) ligands, and Dil-labeled Ac-LDL uptake by microglia was blocked by excess A beta. CHO cells transfected with class A or B SRs showed significantly enhanced uptake of A beta. These results show that microglia express SRs that may play a significant role in the clearance of A beta plaques. Binding to SRs could activate inflammation responses that contribute to the pathology of Alzheimer's disease.
引用
收藏
页码:553 / 565
页数:13
相关论文
共 66 条
  • [1] Identification of scavenger receptor SR-BI as a high density lipoprotein receptor
    Acton, S
    Rigotti, A
    Landschulz, KT
    Xu, SZ
    Hobbs, HH
    Krieger, M
    [J]. SCIENCE, 1996, 271 (5248) : 518 - 520
  • [2] ACTON SL, 1994, J BIOL CHEM, V269, P21003
  • [3] BRAIN MICROGLIA CONSTITUTIVELY EXPRESS BETA-2 INTEGRINS
    AKIYAMA, H
    MCGEER, PL
    [J]. JOURNAL OF NEUROIMMUNOLOGY, 1990, 30 (01) : 81 - 93
  • [4] BETA-AMYLOID STIMULATES GLIAL-CELLS INVITRO TO PRODUCE GROWTH-FACTORS THAT ACCUMULATE IN SENILE PLAQUES IN ALZHEIMERS-DISEASE
    ARAUJO, DM
    COTMAN, CW
    [J]. BRAIN RESEARCH, 1992, 569 (01) : 141 - 145
  • [5] ASHKENAS J, 1993, J LIPID RES, V34, P983
  • [6] UP-REGULATION OF THE MACROPHAGE SCAVENGER RECEPTOR IN RESPONSE TO DIFFERENT FORMS OF INJURY IN THE CNS
    BELL, MD
    LOPEZGONZALEZ, R
    LAWSON, L
    HUGHES, D
    FRASER, I
    GORDON, S
    PERRY, VH
    [J]. JOURNAL OF NEUROCYTOLOGY, 1994, 23 (10): : 605 - 613
  • [7] BURDICK D, 1992, J BIOL CHEM, V267, P546
  • [8] RELEASE OF EXCESS AMYLOID BETA-PROTEIN FROM A MUTANT AMYLOID BETA-PROTEIN PRECURSOR
    CAI, XD
    GOLDE, TE
    YOUNKIN, SG
    [J]. SCIENCE, 1993, 259 (5094) : 514 - 516
  • [9] INVITRO FORMATION OF AMYLOID FIBRILS FROM 2 SYNTHETIC PEPTIDES OF DIFFERENT LENGTHS HOMOLOGOUS TO ALZHEIMERS-DISEASE BETA-PROTEIN
    CASTANO, EM
    GHISO, J
    PRELLI, F
    GOREVIC, PD
    MIGHELI, A
    FRANGIONE, B
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1986, 141 (02) : 782 - 789
  • [10] Christie RH, 1996, AM J PATHOL, V148, P399