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. 2018 Aug 9;13(8):e0201232.
doi: 10.1371/journal.pone.0201232. eCollection 2018.

Differential chemokine expression under the control of peripheral blood mononuclear cells issued from Alzheimer's patients in a human blood brain barrier model

Julie Vérité  1 , Guylène Page  1 , Marc Paccalin  1   2   3 , Adrien Julian  1   3   4 , Thierry Janet  1
Affiliations

Differential chemokine expression under the control of peripheral blood mononuclear cells issued from Alzheimer's patients in a human blood brain barrier model

Julie Vérité et al. PLoS One. .

Abstract

Growing evidence highlights the peripheral blood mononuclear cells (PBMCs) role and the chemokine involvement in the Alzheimer's disease (AD) physiopathology. However, few data are available about the impact of AD PBMCs in the chemokine signature in a brain with AD phenotype. Therefore, this study analyzed the chemokine levels in a human blood brain barrier model. A human endothelial cell line from the immortalized cerebral microvascular endothelial cell line (hCMEC/D3) and a human glioblastoma U-87 MG cell line, both with no AD phenotype were used while PBMCs came from AD at mild or moderate stage and control patients. PBMCs from moderate AD patients decreased CCL2 and CCL5 levels in endothelial, and also CXCL10 in abluminal compartments and in PBMCs compared to PBMCs from mild AD patients. The CX3CL1 expression increased in endothelial and abluminal compartments with PBMCs from mild AD patients compared to controls. AD PBMCs can convert the chemokine signature towards that found in AD brain, targeting some chemokines as new biomarkers in AD.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. CCL2 levels in experimental human BBB models.
CCL2 expression in lysates of PBMCs (PB) (A), in hCMEC/D3 cells (D3) (B) and in U87 cells seeded on the external side of the insert (U87i) (C). PBMCs were extracted from three groups of patients: control patients (n = 11), mild AD patients (n = 13), and moderate AD patients (n = 7). Chemokines were analyzed by the 5-plex Luminex® xMAP® assay containing a mixture of beads specific for each chemokine as described in Methods. Chemokine levels in lysates are expressed in pg/mg protein. The mean is represented by a colored line following PBMCs origins (blue, purple, red for control, mild AD and moderate AD patients, respectively). *P < 0.05 in BBB model with PBMCs from moderate AD patients compared to BBB model with PBMCs from mild AD patients by a Mann-Whitney’s test.
Fig 2
Fig 2. CCL5 levels in experimental human BBB models.
CCL5 expression in the abluminal culture media M2 (A), in hCMEC/D3 cells (D3) (B), in U87 cells seeded on the external side of the insert (U87i) (C) and in U87 cells seeded on bottom wells (U87w) (D). PBMCs were extracted from three groups of patients: control patients (n = 11), mild AD patients (n = 13), and moderate AD patients (n = 7). Chemokines were analyzed by the 5-plex Luminex® xMAP® assay containing a mixture of beads specific for each chemokine as described in Methods. Chemokine levels in lysates are expressed in pg/mg protein, and in pg/mL for culture media. The mean is represented by a colored line following PBMCs origins (blue, purple, red for control, mild AD, and moderate AD patients, respectively). *P < 0.05 in BBB model with PBMCs from moderate AD patients compared to BBB model with PBMCs from mild AD patients by a Mann-Whitney’s test.
Fig 3
Fig 3. CX3CL1 levels in experimental human BBB models.
CX3CL1 expression in the luminal culture media M1 (A), in the abluminal culture media M2 (M2) (B) in U87 cells seeded on the external side of the insert (U87i) (C). PBMCs were extracted from three groups of patients: control patients (n = 11), mild AD patients (n = 13), and moderate AD patients (n = 7). Chemokines were analyzed by the 5-plex Luminex® xMAP® assay containing a mixture of beads specific for each chemokine as described in Methods. Chemokine levels in lysates are expressed in pg/mg protein, and in pg/mL for culture media. The mean is represented by a colored line following PBMCs origins (blue, purple, red for control, mild AD, and moderate AD patients, respectively). *P < 0.05 in BBB model with PBMCs from moderate AD patients compared to BBB model with PBMCs from control patients and †P < 0.05 in BBB model with PBMCs from mild AD patients compared to BBB model with PBMCs from control patients by a Mann-Whitney’s test.
Fig 4
Fig 4. CXCL10 levels in experimental human BBB models.
CXCL10 expression in lysates of PBMCs cells (PB) (A) and in lysates of U87 cells seeded on the external side of the insert (U87i) (B). PBMCs were extracted from three groups of patients: control patients (n = 11), mild AD patients (n = 13), and moderate AD patients (n = 7). Chemokines were analyzed by the 5-plex Luminex® xMAP® assay containing a mixture of beads specific for each chemokine as described in Methods. Chemokine levels in lysates are expressed in pg/mg protein. The mean is represented by a colored line following PBMCs origins (blue, purple, red for control, mild AD and moderate AD patients, respectively). *P < 0.05 in BBB model with PBMCs from moderate AD patients compared to BBB model with PBMCs from mild AD patients by a Mann-Whitney’s test.
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Grants and funding

The authors received no specific funding for this work but authors thank funding supports for the team from the French Ministry of Higher Education and Research, the Memory Resource and Research Centre of Poitiers University Hospital and by a charity association “France Alzheimer Vienne”.