title: Blockade of cannabinoid receptors reduces inflammation, leukocyte accumulation and neovascularization in a model of sponge-induced inflammatory angiogenesis.
abstract: OBJECTIVE
  Angiogenesis depends on a complex interaction between cellular networks and mediators. The endocannabinoid system and its receptors have been shown to play a role in models of inflammation. Here, we investigated whether blockade of cannabinoid receptors may interfere with inflammatory angiogenesis.
  
  
  METHODS
  Polyester-polyurethane sponges were implanted in C57Bl/6j mice. Animals received doses (3 and 10 mg/kg/daily, s.c.) of the cannabinoid receptor antagonists SR141716A (CB1) or SR144528 (CB2). Implants were collected at days 7 and 14 for cytokines, hemoglobin, myeloperoxidase, and N-acetylglucosaminidase measurements, as indices of inflammation, angiogenesis, neutrophil and macrophage accumulation, respectively. Histological and morphometric analysis were also performed.
  
  
  RESULTS
  Cannabinoid receptors expression in implants was detected from day 4 after implantation. Treatment with CB1 or CB2 receptor antagonists reduced cellular influx into sponges at days 7 and 14 after implantation, although CB1 receptor antagonist were more effective at blocking leukocyte accumulation. There was a reduction in TNF-α, VEGF, CXCL1/KC, CCL2/JE, and CCL3/MIP-1α levels, with increase in CCL5/RANTES. Both treatments reduced neovascularization. Dual blockade of cannabinoid receptors resulted in maximum inhibition of inflammatory angiogenesis.
  
  
  CONCLUSIONS
  Blockade of cannabinoid receptors reduced leukocyte accumulation, inflammation and neovascularization, suggesting an important role of endocannabinoids in sponge-induced inflammatory angiogenesis both via CB1 and CB2 receptors.
authors.affiliation: Departamento de Bioquímica e Imunologia-ICB, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil. rguabiraba@gmail.com
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Guabiraba
authors.forename: Remo C
authors.initials: RC
authors.lastname: Russo
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Coelho
authors.forename: Mônica A N D
authors.initials: MA
authors.lastname: Ferreira
authors.forename: Gabriel A O
authors.initials: GA
authors.lastname: Lopes
authors.forename: Ariane K C
authors.initials: AK
authors.lastname: Gomes
authors.forename: Silvia P
authors.initials: SP
authors.lastname: Andrade
authors.forename: Luciola S
authors.initials: LS
authors.lastname: Barcelos
authors.forename: Mauro M
authors.initials: MM
authors.lastname: Teixeira
mesh_terms: D000818:Animals; D001892:Camphanes / Q000494:pharmacology; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology; D016207:Cytokines / Q000276:immunology; D005547:Foreign Bodies / Q000276:immunology*; D005549:Foreign-Body Reaction / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D007962:Leukocytes / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D010880:Piperidines / Q000494:pharmacology; D011091:Polyesters; D011140:Polyurethanes; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000276:immunology*; D043885:Receptor, Cannabinoid, CB2 / Q000276:immunology*; D000077285:Rimonabant; D012867:Skin / Q000276:immunology
chemical_list: D001892:Camphanes; D063387:Cannabinoid Receptor Antagonists; D016207:Cytokines; D010880:Piperidines; D011091:Polyesters; D011140:Polyurethanes; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; C110630:SR 144528; D000077285:Rimonabant