Prolonged Morphine Exposure Induces Increased Firm Adhesion in an in Vitro Model of the Blood-Brain Barrier.
The blood-brain barrier (BBB) has been defined as a critically important protective barrier that is involved in providing essential biologic, physiologic, and immunologic separation between the central nervous system (CNS) and the periphery. Insults to the BBB can cause overall barrier damage or deregulation of the careful homeostasis maintained between the periphery and the CNS. These insults can, therefore, yield numerous phenotypes including increased overall permeability, interendothelial gap formation, alterations in cytokine and chemokine secretion, and accelerated cellular passage. The current studies expose the human brain microvascular endothelial cell line, hCMEC/D3, to prolonged morphine exposure and aim to uncover the mechanisms underlying alterations in barrier function in vitro. These studies show alterations in the mRNA and protein levels of the cellular adhesion molecules (CAMs) intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and activated leukocyte cell adhesion molecule that correlate with an increased firm adhesion of the CD3⁺ subpopulation of peripheral blood mononuclear cells (PBMCs). Overall, these studies suggest that prolonged morphine exposure may result in increased cell migration into the CNS, which may accelerate pathological processes in many diseases that involve the BBB.
Department of Microbiology and Immunology, and Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19102, USA. ms996@drexel.edu.
Marianne
M
Strazza
Department of Microbiology and Immunology, and Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19102, USA. vpirrone@drexelmed.edu.
Vanessa
V
Pirrone
Department of Microbiology and Immunology, and Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19102, USA. bwigdahl@drexelmed.edu.|Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA. bwigdahl@drexelmed.edu.
Brian
B
Wigdahl
Department of Microbiology and Immunology, and Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19102, USA. wnd22@drexel.edu.
Will
W
Dampier
School of Mathematical Sciences and Center for Statistical Science, Peking University, Beijing 100871, China. weilin@math.pku.edu.cn.
Wei
W
Lin
Department of Biostatistics and Epidemiology, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. ruifeng@upenn.edu.
Rui
R
Feng
Department of Microbiology and Immunology, and Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19102, USA. mem446@drexel.edu.
Monique E
ME
Maubert
Department of Medicine, Division of Hematology and Oncology, Weill Cornell Medical College, New York, NY 10065, USA. babette@med.cornell.edu.
Babette
B
Weksler
Department of Biological Sciences, Open University, Walton Hall, Milton Keynes MK7 6AA, UK. i.romero@open.ac.uk.
Ignacio A
IA
Romero
Institut Cochin, INSERM (Institut National de la Sant&#233; et de la Recherche M&#233;dicale), U1016, CNRS UMR8104, Universit&#233; Paris Descartes, Sorbonne Paris Cit&#233;, Paris 75014, France. pierre-olivier.couraud@inserm.fr.
Pierre-Olivier
PO
Couraud
Department of Microbiology and Immunology, and Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19102, USA. mnonnema@drexelmed.edu.
Michael R
MR
Nonnemacher
D000701:Analgesics, Opioid / Q000009:adverse effects / Q000494:pharmacology*; D001812:Blood-Brain Barrier / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D009020:Morphine / Q000009:adverse effects / Q000494:pharmacology*
D000701:Analgesics, Opioid; D015815:Cell Adhesion Molecules; D009020:Morphine
(peripheral blood mononuclear cell) PBMC; blood–brain barrier; brain microvascular endothelial cells (BMEC); cellular adhesion molecules (CAM); morphine