title: Long-lasting priming of endothelial cells by plasma melatonin levels.
abstract: BACKGROUND
  Endothelial cells are of great interest for cell therapy and tissue engineering. Understanding the heterogeneity among cell lines originating from different sources and culture protocols may allow more standardized material to be obtained. In a recent paper, we showed that adrenalectomy interferes with the expression of membrane adhesion molecules on endothelial cells maintained in culture for 16 to 18 days. In addition, the pineal hormone, melatonin, reduces the adhesion of neutrophils to post-capillary veins in rats. Here, we evaluated whether the reactivity of cultured endothelial cells maintained for more than two weeks in culture is inversely correlated to plasma melatonin concentration.
  
  
  RESULTS
  The nocturnal levels of melatonin were manipulated by treating rats with LPS. Nocturnal plasma melatonin, significantly reduced two hours after LPS treatment, returned to control levels after six hours. Endothelial cells obtained from animals that had lower nocturnal melatonin levels significantly express enhanced adhesion molecules and iNOS, and have more leukocytes adhered than cells from animals that had normal nocturnal levels of melatonin (naïve or injected with vehicle). Endothelial cells from animals sacrificed two hours after a simultaneous injection of LPS and melatonin present similar phenotype and function than those obtained from control animals. Analyzing together all the data, taking into account the plasma melatonin concentration versus the expression of adhesion molecules or iNOS we detected a significant inverse correlation.
  
  
  CONCLUSIONS
  Our data strongly suggest that the plasma melatonin level primes endothelial cells "in vivo," indicating that the state of the donor animal is translated to cells in culture and therefore, should be considered for establishing cell banks in ideal conditions.
authors.affiliation: Laboratory of Chronopharmacology, Department of Physiology, Institute of Bioscience, Universidade de São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Eduardo Koji
authors.initials: EK
authors.lastname: Tamura
authors.forename: Pedro Augusto
authors.initials: PA
authors.lastname: Fernandes
authors.forename: Marina
authors.initials: M
authors.lastname: Marçola
authors.forename: Sanseray
authors.initials: S
authors.lastname: da Silveira Cruz-Machado
authors.forename: Regina Pekelmann
authors.initials: RP
authors.lastname: Markus
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D002940:Circadian Rhythm / Q000502:physiology*; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008550:Melatonin / Q000097:blood*; D009504:Neutrophils / Q000166:cytology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D008070:Lipopolysaccharides; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D052247:Nitric Oxide Synthase Type II; D008550:Melatonin