title: The leukocyte-endothelial cell interactions are modulated by extracellular matrix proteins.
abstract: BACKGROUND
  Endothelium is supported, in normal conditions, by a basement membrane composed, among others, by collagen IV and laminin. Changes in the basement membrane composition could induce changes in endothelial cell modifying their interactions with leukocytes.
  
  
  RESULTS
  Isolated polymorphonuclear cells (PMN) and peripheral blood mononuclear cells (PBMC) were added to cultured human umbilical endothelial cells (HuVEC) previously seeded on collagen IV, collagen I or gelatin. Adhesion of leukocytes to HUVEC and specific cytotoxicity were analysed. PMN adhesion and cytotoxicity were lower whereas those from PBMC were higher when HuVEC were seeded on collagen I, as compared with cells seeded on collagen IV. To analyse the mechanisms involved in these phenomena, P-selectin, ICAM-1, VCAM-1 and MCP- 1 expression were evaluated in HuVEC seeded on the different ECM components. P-selectin and mRNA expression of VCAM-1 were lower in cells seeded on collagen I. By contrast, MCP-1 expression was higher in collagen I. Collagen I-dependent effects were partially prevented when collagen I was treated with pepsin. ILK activity was lower in cells seeded on collagen I, whereas ERK 1/2 activity was enhanced. ILK overexpression reduced ERK 1/2 phosphorylation and this could promote the reduction in P-selectin and the increase in MCP-1.
  
  
  CONCLUSIONS
  Collagen I decreased ILK activity and this would induce an increase in ERK 1/2 activity in HuVEC. As a consequence, the P-selectin content is diminished and, by contrast, the MCP-1 content is increased. The final effect is a lower recruitment of PMN and a higher adhesion of PBMC.
authors.affiliation: Department of Physiology, Alcala University, Madrid, Spain. mpiedad.ruiz@uah.es
authors.forename: María P
authors.initials: MP
authors.lastname: Ruiz-Torres
authors.forename: Gema
authors.initials: G
authors.lastname: Pérez-Rivero
authors.forename: Manuel
authors.initials: M
authors.lastname: Rodríguez-Puyol
authors.forename: Diego
authors.initials: D
authors.lastname: Rodríguez-Puyol
authors.forename: Maria L
authors.initials: ML
authors.lastname: Díez-Marqués
mesh_terms: D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication / Q000502:physiology*; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007962:Leukocytes / Q000166:cytology* / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D019007:P-Selectin / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics; D000099200:Scaffold Protein ILK
chemical_list: D018932:Chemokine CCL2; D003094:Collagen; D016326:Extracellular Matrix Proteins; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D019007:P-Selectin; D017346:Protein Serine-Threonine Kinases; D019010:Vascular Cell Adhesion Molecule-1; D000099200:Scaffold Protein ILK; C111835:CCL2 protein, human