title: Transendothelial migration of lymphocytes mediated by intraendothelial vesicle stores rather than by extracellular chemokine depots.
abstract: Chemokines presented by the endothelium are critical for integrin-dependent adhesion and transendothelial migration of naive and memory lymphocytes. Here we found that effector lymphocytes of the type 1 helper T cell (T(H)1 cell) and type 1 cytotoxic T cell (T(C)1 cell) subtypes expressed adhesive integrins that bypassed chemokine signals and established firm arrests on variably inflamed endothelial barriers. Nevertheless, the transendothelial migration of these lymphocytes strictly depended on signals from guanine nucleotide-binding proteins of the G(i) type and was promoted by multiple endothelium-derived inflammatory chemokines, even without outer endothelial surface exposure. Instead, transendothelial migration-promoting endothelial chemokines were stored in vesicles docked on actin fibers beneath the plasma membranes and were locally released within tight lymphocyte-endothelial synapses. Thus, effector T lymphocytes can cross inflamed barriers through contact-guided consumption of intraendothelial chemokines without surface-deposited chemokines or extraendothelial chemokine gradients.
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Ziv
authors.initials: Z
authors.lastname: Shulman
authors.forename: Shmuel J
authors.initials: SJ
authors.lastname: Cohen
authors.forename: Ben
authors.initials: B
authors.lastname: Roediger
authors.forename: Vyacheslav
authors.initials: V
authors.lastname: Kalchenko
authors.forename: Rohit
authors.initials: R
authors.lastname: Jain
authors.forename: Valentin
authors.initials: V
authors.lastname: Grabovsky
authors.forename: Eugenia
authors.initials: E
authors.lastname: Klein
authors.forename: Vera
authors.initials: V
authors.lastname: Shinder
authors.forename: Liat
authors.initials: L
authors.lastname: Stoler-Barak
authors.forename: Sara W
authors.initials: SW
authors.lastname: Feigelson
authors.forename: Tsipi
authors.initials: T
authors.lastname: Meshel
authors.forename: Susanna M
authors.initials: SM
authors.lastname: Nurmi
authors.forename: Itamar
authors.initials: I
authors.lastname: Goldstein
authors.forename: Olivier
authors.initials: O
authors.lastname: Hartley
authors.forename: Carl G
authors.initials: CG
authors.lastname: Gahmberg
authors.forename: Amos
authors.initials: A
authors.lastname: Etzioni
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Weninger
authors.forename: Adit
authors.initials: A
authors.lastname: Ben-Baruch
authors.forename: Ronen
authors.initials: R
authors.lastname: Alon
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D016023:Integrins / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D054390:Receptors, CCR2 / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D057705:Transendothelial and Transepithelial Migration / Q000276:immunology*; D022161:Transport Vesicles / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014657:Vasculitis / Q000276:immunology / Q000378:metabolism
chemical_list: D018925:Chemokines; D018960:Hyaluronan Receptors; D016023:Integrins; D054390:Receptors, CCR2; D014409:Tumor Necrosis Factor-alpha; D019206:GTP-Binding Protein alpha Subunits, Gi-Go