title: Substance P-neurokinin-1 receptor interaction upregulates monocyte tissue factor.
abstract: Monocytes play an important role in hemostasis. In this study, the prothrombotic effects of the neuropeptide substance P (SP) on human monocytes through neurokinin-1 receptor (NK1-R) were characterized. SP upregulated monocyte tissue factor (TF), the major coagulation cascade stimulator, in a concentration and time dependent manner. Specific inhibition of NK1-R completely blocked TF expression. Monocytes stimulated by SP released cytokines and chemokines. When monocytes were stimulated with cytokines or chemokines, TF was expressed by the cytokines (GM-CSF, IFN-γ and TNF-α). Cytokines may play a major role in the mechanism of SP induced monocyte TF expression. NK1-R antagonists (NK1-RA) may have a role in developing novel therapeutic approaches to patients vulnerable to vaso-occlusive disorders.
authors: Department of Psychiatry and Behavioral Sciences, Children's Hospital of Philadelphia Research Institute, Philadelphia, PA, United States.
authors: Mohammad M
authors: MM
authors: Khan
authors: Steven D
authors: SD
authors: Douglas
authors: Tami D
authors: TD
authors: Benton
mesh_terms: D001779:Blood Coagulation Factors / Q000502:physiology; D004306:Dose-Response Relationship, Immunologic; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D064729:Neurokinin-1 Receptor Antagonists; D009479:Neuropeptides / Q000502:physiology*; D018040:Receptors, Neurokinin-1 / Q000502:physiology*; D013373:Substance P / Q000502:physiology*; D013925:Thromboplastin / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D015854:Up-Regulation / Q000276:immunology*
chemical_list: D001779:Blood Coagulation Factors; D064729:Neurokinin-1 Receptor Antagonists; D009479:Neuropeptides; D018040:Receptors, Neurokinin-1; D014409:Tumor Necrosis Factor-alpha; D013373:Substance P; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013925:Thromboplastin