title: Focal effects of mononuclear leukocyte transendothelial migration: TNF-alpha production by migrating monocytes promotes subsequent migration of lymphocytes.
abstract: In many inflammatory diseases, mononuclear leukocytes (MNLs) accumulate as focal infiltrates in perivascular spaces. We postulated that MNLs migrating through endothelium modify the microenvironment to promote the subsequent migration of additional MNLs into the same area. We found that as monocytes adhere to and migrate spontaneously through an endothelial monolayer, they secrete tumor necrosis factor-alpha (TNF-alpha) and interleukin-1. These cytokines stimulate endothelial cell expression of CD54 (intercellular adhesion molecule-1) and CD106 (vascular cell adhesion molecule-1). Consequently, when freshly isolated MNLs are added to that endothelial monolayer four or more hours later, significantly greater numbers of lymphocytes bind to and migrate through these endothelial monolayers. In addition to its ability to activate endothelial cell adhesion molecules, TNF-alpha induced directed migration of lymphocytes through collagen pads. These results illustrate a potential amplification mechanism by which MNLs moving through a vessel wall may secrete TNF-alpha, leading to the recruitment of additional leukocytes into the same perivascular locus.
authors.affiliation: Research Center for AIDS and HIV Infections, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: de Jong
authors.forename: D M
authors.initials: DM
authors.lastname: Green
authors.forename: J A
authors.initials: JA
authors.lastname: Trial
authors.forename: H H
authors.initials: HH
authors.lastname: Birdsall
mesh_terms: D002450:Cell Communication; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004730:Endothelium, Vascular / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000096:biosynthesis; D007375:Interleukin-1 / Q000096:biosynthesis; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000502:physiology*; D008214:Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000494:pharmacology; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis / Q000096:biosynthesis
chemical_list: D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1