Neuropeptide Y upregulates the adhesiveness of human endothelial cells for leukocytes.
The nervous system and the autonomic system in particular have been associated with stress-induced changes in host resistance to infections and inflammatory reactions. Since a key step in initiation of inflammation is adhesion of leukocytes to the endothelium, we hypothesized that neuron-derived factors might be involved in this process. Neuropeptide Y (NPY), a 36-amino acid neuropeptide that is colocalized and released with norepinephrine from sympathetic nerves, has already been implicated in inflammatory reactions via modulation of histamine release from mast cells. This study was undertaken to examine the potential role of NPY in proinflammatory processes via modulation of endothelium-leukocyte interaction. NPY (0.01-10 microM) increased the adhesion of 51Cr-labeled human neutrophils or the human monocytic U937 cell line to human umbilical vein endothelial cells in a dose- and time-dependent manner. The stimulation of human umbilical vein endothelial cell adhesiveness occurred as early as 30 minutes and lasted over 48 hours. The increase of leukocyte adhesion to human umbilical vein endothelial cells by NPY was not inhibited by protein synthesis inhibitor cycloheximide, nor was it associated with expression of intercellular adhesion molecule-1 on human umbilical vein endothelial cells; in contrast, strong expression of intercellular adhesion molecule-1 was induced by tumor necrosis factor alpha and lipopolysaccharide endotoxin. These data suggest that neuron-derived factors such as NPY may serve as modulators of not only the neuromuscular unit but also the interaction of endothelial cells with leukocytes. In this capacity, the sympathetic nervous system might play an important role in the regulation of proaggregatory and hemostatic activity of microvessels.
Sung
C P
CP
Department of Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406.
Arleth
A J
AJ
Feuerstein
G Z
GZ
D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007962:Leukocytes / Q000378:metabolism / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000502:physiology; D009478:Neuropeptide Y / Q000494:pharmacology / Q000502:physiology*; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015815:Cell Adhesion Molecules; D009478:Neuropeptide Y; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1