title: CXCL1 contributes to β-amyloid-induced transendothelial migration of monocytes in Alzheimer's disease.
abstract: BACKGROUND
  Bone marrow-derived microglia that originates in part from hematopoietic cells, and more particularly from monocytes preferentially attach to amyloid deposition in brains of Alzheimer's disease (AD). However, the mechanism of monocytes recruited into the amyloid plaques with an accelerated process in AD is unclear.
  
  
  RESULTS
  Here we reported that monocytes from AD patients express significantly higher chemokine (C-X-C motif) ligand 1 (CXCL1) compared to age-matched controls. AD patient's monocytes or CXCL1-overexpressing THP-1 cells had enhanced ability of β-amyloid (Aβ)-induced transendothelial migration and Aβ-induced transendothelial migration for AD patient's monocytes or CXCL1-overexpressing THP-1 cells was almost abrogated by anti-CXCL1 antibody. Furthermore, monocytes derived from a transgenic mouse model of AD also expressed significantly higher CXCL1. CD11b⁺CD45(hi) population of cells that were recruited from the peripheral blood were markedly bolcked in APP mouse brain by anti-CXCL1 antibody. Accordingly, in response to Aβ, human brain microvascular endothelial cells (HBMEC) significantly up-regulated CXC chemokine receptor 2 (CXCR2) expression, which was the only identified receptor for CXCL1. In addition, a high level expression of CXCR2 in HBMEC significantly promoted the CXCL1-overexpressing THP-1 cells transendothelial migration, which could be was abrogated by anti-CXCR2 antibody. Further examination of possible mechanisms found that CXCL1-overexpressing THP-1 cells induced transendothelial electrical resistance decrease, horseradish peroxidase flux increase, ZO-1 discontinuous and occludin re-distribution from insoluble to soluble fraction through interacting with CXCR2. ROCK inhibitor, Y27632, could block CXCL1-overexpressing THP-1 cells transendothelial migration, whereas other inhibitors had no effects.
  
  
  CONCLUSIONS
  The present data indicate that monocytes derived from AD patients overexpressing CXCL1, which is a determinant for Aβ-induced transendothelial migration. CXCL1 expressed by monocytes and CXCR2 on HBMEC is involved in monocytes migrating from blood to brain in AD patients.
authors: Department of Developmental Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.
authors: Ke
authors: K
authors: Zhang
authors: Li
authors: L
authors: Tian
authors: Li
authors: L
authors: Liu
authors: Yu
authors: Y
authors: Feng
authors: Yan-Bin
authors: YB
authors: Dong
authors: Bo
authors: B
authors: Li
authors: De-Shu
authors: DS
authors: Shang
authors: Wen-Gang
authors: WG
authors: Fang
authors: Yun-Peng
authors: YP
authors: Cao
authors: Yu-Hua
authors: YH
authors: Chen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology; D001921:Brain / Q000473:pathology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D054360:Chemokine CXCL1 / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000473:pathology*; D023063:Receptors, Interleukin-8B / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism; D057705:Transendothelial and Transepithelial Migration / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D054360:Chemokine CXCL1; D023063:Receptors, Interleukin-8B; D054460:rho-Associated Kinases; D020741:rho GTP-Binding Proteins
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