β-Amyloid-induced migration of monocytes across human brain endothelial cells involves RAGE and PECAM-1

Ranjit Giri, Yamin Shen, Monique Stins, Shi Du Yan, Ann Marie Schmidt, David Stern, Kwang Sik Kim, Berislav Zlokovic, Vijay K. Kalra

Research output: Contribution to journalArticle

160 Citations (Scopus)

Abstract

In patients with amyloid β-related cerebrovascular disorders, e.g., Alzheimer's disease, one finds increased deposition of amyloid peptide (Aβ) and increased presence of monocyte/microglia cells in the brain. However, relatively little is known of the role of Aβ in the trafficking of monocytes across the blood-brain barrier (BBB). Our studies show that interaction of Aβ1-40 with monolayer of human brain endothelial cells results in augmented adhesion and transendothelial migration of monocytic cells (THP-1 and HL-60) and peripheral blood monocytes. The Aβ-mediated migration of monocytes was inhibited by antibody to Aβ receptor (RAGE) and platelet endothelial cell adhesion molecule (PECAM-1). Additionally, Aβ-induced transendothelial migration of monocytes were inhibited by protein kinase C inhibitor and augmented by phosphatase inhibitor. We conclude that interaction of Aβ with RAGE expressed on brain endothelial cells initiates cellular signaling leading to the transendothelial migration of monocytes. We suggest that increased diapedesis of monocytes across the BBB in response to Aβ present either in the peripheral circulation or in the brain parenchyma may play a role in the pathophysiology of Aβ-related vascular disorder.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume279
Issue number6 48-6
StatePublished - Dec 28 2000
Externally publishedYes

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CD31 Antigens
Amyloid
Monocytes
Endothelial Cells
Transendothelial and Transepithelial Migration
Brain
Blood-Brain Barrier
Cerebrovascular Disorders
Protein C Inhibitor
Microglia
Protein Kinase Inhibitors
Phosphoric Monoester Hydrolases
Protein Kinase C
Blood Vessels
Alzheimer Disease
Antibodies

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cell Biology

Cite this

β-Amyloid-induced migration of monocytes across human brain endothelial cells involves RAGE and PECAM-1. / Giri, Ranjit; Shen, Yamin; Stins, Monique; Yan, Shi Du; Schmidt, Ann Marie; Stern, David; Kim, Kwang Sik; Zlokovic, Berislav; Kalra, Vijay K.

In: American Journal of Physiology - Cell Physiology, Vol. 279, No. 6 48-6, 28.12.2000.

Research output: Contribution to journalArticle

Giri, R, Shen, Y, Stins, M, Yan, SD, Schmidt, AM, Stern, D, Kim, KS, Zlokovic, B & Kalra, VK 2000, 'β-Amyloid-induced migration of monocytes across human brain endothelial cells involves RAGE and PECAM-1', American Journal of Physiology - Cell Physiology, vol. 279, no. 6 48-6.
Giri, Ranjit ; Shen, Yamin ; Stins, Monique ; Yan, Shi Du ; Schmidt, Ann Marie ; Stern, David ; Kim, Kwang Sik ; Zlokovic, Berislav ; Kalra, Vijay K. / β-Amyloid-induced migration of monocytes across human brain endothelial cells involves RAGE and PECAM-1. In: American Journal of Physiology - Cell Physiology. 2000 ; Vol. 279, No. 6 48-6.
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AU - Schmidt, Ann Marie

AU - Stern, David

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