Chlamydia pneumoniae infection promotes the transmigration of monocytes through human brain endothelial cells.
We have investigated the effects of Chlamydia pneumoniae on human brain endothelial cells (HBMECs) and human monocytes as a mechanism for breaching the blood-brain barrier (BBB) in Alzheimer's disease (AD). HBMECs and peripheral blood monocytes may be key components in controlling the entry of C. pneumoniae into the human brain. Our results indicate that C. pneumoniae infects blood vessels and monocytes in AD brain tissues compared with normal brain tissue. C. pneumoniae infection stimulates transendothelial entry of monocytes through HBMECs. This entry is facilitated by the up-regulation of VCAM-1 and ICAM-1 on HBMECs and a corresponding increase of LFA-1, VLA-4, and MAC-1 on monocytes. C. pneumoniae infection in HBMECs and THP-1 monocytes up-regulates monocyte transmigration threefold in an in vitro brain endothelial monolayer. In this way, C. pneumoniae infection in these cell types may contribute to increased monocyte migration and promote inflammation within the CNS resulting from infection at the level of the vasculature. Thus, infection at the level of the vasculature may be a key initiating factor in the pathogenesis of neurodegenerative diseases such as sporadic AD.
MacIntyre
A
A
Department of Biomedical Sciences, Philadelphia College of Osteopathic Medicine, Philadelphia, Pennsylvania, USA.
Abramov
R
R
Hammond
C J
CJ
Hudson
A P
AP
Arking
E J
EJ
Little
C S
CS
Appelt
D M
DM
Balin
B J
BJ
D000544:Alzheimer Disease / Q000150:complications* / Q000382:microbiology / Q000473:pathology; D001812:Blood-Brain Barrier / Q000276:immunology; D001921:Brain / Q000098:blood supply / Q000382:microbiology / Q000473:pathology; D002452:Cell Count; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D023521:Chlamydophila Infections / Q000150:complications* / Q000382:microbiology / Q000473:pathology; D016993:Chlamydophila pneumoniae / Q000302:isolation & purification; D004730:Endothelium, Vascular / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology*; D005434:Flow Cytometry; D006801:Humans; D039041:Integrin alpha4beta1 / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism; D009000:Monocytes / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D015854:Up-Regulation / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D039041:Integrin alpha4beta1; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1