title: Granulocyte colony-stimulating factor increases expression of adhesion receptors on endothelial cells through activation of p38 MAPK.
abstract: OBJECTIVE
  Granulocyte colony-stimulating factor (G-CSF) is specific for the granulocytic cell line, although receptors for this cytokine have been found in other cell types including endothelial cells. These observations prompted us to investigate the potential effect of G-CSF on the endothelium. DESIGN AN METHODS: Endothelial cell monolayers were exposed to G-CSF to evaluate: i) signal transduction mechanisms, ii) expression of adhesion receptors at the cell surface, and iii) leukocyte adhesion on EC monolayers.
  
  
  RESULTS
  Exposure of human umbilical vein endothelial cells (EC) in culture to G-CSF resulted in the activation of the signal transduction pathways JAK/STAT (JAK-1, STAT-1 and STAT-3) and RAS/MAPK (MAPK p42/44 and p38 MAPK). We also observed significantly increased expression of the adhesion receptors, E-selectin (ELAM-1), vascular endothelial cell adhesion molecule-1 and intracelleular adhesion molecule-1 at the cell surface in response to G-CSF, increases that were followed by an augmented adhesion of leukocytes on the previously exposed EC monolayers. These effects were blocked by the presence of SB203580, a p38 MAPK inhibitor, by U0126, a MAPK p42/44 inhibitor, and by inhibiting the G-CSF receptor with a specific antibody.
  
  
  CONCLUSIONS
  Our results demonstrate that G-CSF increases the expression of adhesion receptors on EC, promoting leukocyte adhesion. This effect seems to be triggered by the signaling events that follow receptor binding. Results from experiments using specific inhibitors suggest that activation of p38 MAPK is required to promote expression of adhesion receptors in endothelial cells and the recruitment of leukocytes in response to G-CSF.
authors.affiliation: Servicio de Hemoterapia-Hemostasia, Hospital Clínic, IDIBAPS, Barcelona, Spain.
authors.forename: Berta
authors.initials: B
authors.lastname: Fusté
authors.forename: Roberto
authors.initials: R
authors.lastname: Mazzara
authors.forename: Ginés
authors.initials: G
authors.lastname: Escolar
authors.forename: Anna
authors.initials: A
authors.lastname: Merino
authors.forename: Antonio
authors.initials: A
authors.lastname: Ordinas
authors.forename: Maribel
authors.initials: M
authors.lastname: Díaz-Ricart
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000502:physiology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000166:cytology*; D004789:Enzyme Activation / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D047468:Immunoprecipitation; D007962:Leukocytes / Q000502:physiology; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; D016179:Granulocyte Colony-Stimulating Factor; D048051:p38 Mitogen-Activated Protein Kinases