title: CC chemokines and transmigration of eosinophils in the presence of vascular cell adhesion molecule 1.
abstract: BACKGROUND
  Interaction between eosinophil alpha4 integrin and vascular cell adhesion molecule 1 (VCAM-1) expressed on activated endothelial cells may be a key step in the selective recruitment of eosinophils from the circulation to sites of inflammation.
  
  
  OBJECTIVE
  To investigate the factor(s) that induces transmigration of eosinophils after firm adhesion via the alpha4 integrin/VCAM-1 pathway.
  
  
  METHODS
  We examined the effects of a variety of inflammatory mediators on the migration of eosinophils across recombinant human (rh) intracellular adhesion molecule 1- or rhVCAM-1-coated Transwell filters or VCAM-1-expressing human pulmonary microvascular endothelial cells (HPMECs) that had been stimulated with interleukin 4 (IL-4) and tumor necrosis factor alpha. The number of eosinophils that had transmigrated was evaluated by measuring eosinophil peroxidase activity.
  
  
  RESULTS
  The CC chemokines RANTES (regulated on activation, normal T-cell expressed, and secreted), eotaxin, eotaxin 2, monocyte chemotactic protein 3 (MCP-3), and MCP-4 each increased eosinophil transmigration across rhVCAM-1-coated filters compared with fetal calf serum-blocked or rh intracellular adhesion molecule 1-coated filters (P < .01). On the other hand, platelet-activating factor, C5a, formyl-methionyl-leucil-phenylalanine, granulocyte-macrophage colony-stimulating factor, IL-5, and IL-8 did not enhance migration across rhVCAM-1. The enhancement of migration by RANTES in the presence of rhVCAM-1 was blocked by an anti-alpha4 integrin monoclonal antibody. CC chemokines augmented eosinophil transmigration across VCAM-1-expressing HPMECs compared with resting HPMECs (P < .01). Conversely, the transmigration induced by platelet-activating factor, C5a, formyl-methionyl-leucil-phenylalanine, or IL-8 was not modified by the expression of VCAM-1 on HPMECs.
  
  
  CONCLUSIONS
  CC chemokines induce transendothelial migration of eosinophils after interaction between eosinophil alpha4 integrin and endothelial VCAM-1.
authors.affiliation: Keiyo Clinic of Internal Medicine, Chiba, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Makoto
authors.initials: M
authors.lastname: Nagata
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Sakamoto
mesh_terms: D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D019742:Chemokines, CC / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D039441:Integrin alpha4 / Q000378:metabolism; D015847:Interleukin-4 / Q000494:pharmacology; D011994:Recombinant Proteins / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D019742:Chemokines, CC; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D039441:Integrin alpha4; D015847:Interleukin-4