title: Δ(9)-Tetrahydrocannabinol (THC) enhances lipopolysaccharide-stimulated tissue factor in human monocytes and monocyte-derived microvesicles.
abstract: BACKGROUND
  Immunomodulatory effects in humans of Δ(9-)Tetrahydrocannabinol (THC), the psychoactive component of marijuana are controversial. Tissue factor (TF), the activator of the extrinsic coagulation cascade, is increased on circulating activated monocytes and is expressed on microvesicles released from activated monocytes during inflammatory conditions, which perpetuate coagulopathies in a number of diseases. In view of the increased medicinal use of marijuana, effects of THC on human monocytes and monocyte-derived microvesicles activated by lipopolysaccharide (LPS) were investigated.
  
  
  RESULTS
  Peak levels of TF procoagulant activity developed in monocytes or microvesicles 6 h following LPS treatment and were unaltered by THC. After 24 h of LPS stimulation, TF activity declined in control-treated or untreated cells and microvesicles, but persisted with THC treatment. Peak TF protein occurred within 6 h of LPS treatment independent of THC; by 24 h, TF protein declined to almost undetectable levels without THC, but was about 4-fold greater with THC. Steady-state TF mRNA levels were similar up to 2 h in the presence of LPS with or without THC, while 10-fold greater TF mRNA levels persisted over 3-24 h with THC treatment. Activation of MAPK or NF-κB pathways was unaltered by THC treatment and inflammatory cytokine IL-6 levels were unchanged. In contrast, TNF and IL-8 levels were enhanced by 20-50 %.
  
  
  CONCLUSIONS
  THC enhances TF expression in activated monocytes resulting in elevated procoagulant activity. Marijuana use could potentiate coagulopathies in individuals with chronic immune activation such as HIV-1 infection or inflammatory bowel disease.
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, 2033 Mowry Road, Gainesville, FL 32610-3663 USA.
authors.forename: Julie C
authors.initials: JC
authors.lastname: Williams
authors.affiliation: Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL USA.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Klein
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, 2033 Mowry Road, Gainesville, FL 32610-3663 USA.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Goldberger
authors.affiliation: Department of Pediatrics, Division of Allergy, Immunology and Rheumatology, School of Medicine, Duke University, Durham, NC USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Sleasman
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, McAlister Heart Institute, University of North Carolina, Chapel Hill, NC USA.
authors.forename: Nigel
authors.initials: N
authors.lastname: Mackman
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, 2033 Mowry Road, Gainesville, FL 32610-3663 USA.
authors.forename: Maureen M
authors.initials: MM
authors.lastname: Goodenow
keywords: Lipopolysaccharide; Marijuana; Monocyte; THC; Tissue factor