title: Transendothelial migration and trafficking of leukocytes in LFA-1-deficient mice.
abstract: The leukocyte integrin LFA-1 plays an important role in leukocyte trafficking and the immune response. Using LFA-1-deficient mice, we demonstrate that LFA-1 regulates the trafficking of lymphocytes to peripheral lymph nodes, and, to a lesser degree, to mesenteric lymph nodes and acute inflammatory sites. LFA-1, either because of its role in initial adhesion and/ or the passage of leukocytes across endothelial cells, plays a vital role in T lymphocyte and neutrophil transendothelial migration. Neutrophils and activated T lymphocytes from LFA-1-deficient mice were unable to cross endothelial cell monolayers in response to a chemokine gradient, whereas wild-type (WT) T lymphocytes and neutrophils were capable of migration. By contrast, LFA-1-deficient T lymphocytes displayed normal chemotaxis to the same chemokine. Our studies with LFA-1-deficient monocytes indicate that LFA-1 acts in concert with complement receptor 3 to mediate transendothelial migration of these cells, as anti-CD18 monoclonal antibodies (mAb) blocked both WT and LFA-1-deficient monocyte transendothelial migration, whereas anti-CD11 b mAb preferentially blocked transendothelial migration of LFA-1-deficient monocytes. Finally, whereas anti-CD31 mAb blocked WT monocyte and neutrophil transendothelial cell migration they did not block LFA-1-deficient monocyte and neutrophil transendothelial migration.
authors.affiliation: Amgen Inc., Boulder, USA. dpandrew@hotmail.com
authors.forename: D P
authors.initials: DP
authors.lastname: Andrew
authors.forename: J P
authors.initials: JP
authors.lastname: Spellberg
authors.forename: H
authors.initials: H
authors.lastname: Takimoto
authors.forename: R
authors.initials: R
authors.lastname: Schmits
authors.forename: T W
authors.initials: TW
authors.lastname: Mak
authors.forename: M M
authors.initials: MM
authors.lastname: Zukowski
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002448:Cell Adhesion; D002465:Cell Movement; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D006968:Hypersensitivity, Delayed; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism; D007962:Leukocytes / Q000502:physiology; D008198:Lymph Nodes; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D016177:Macrophage-1 Antigen / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology*
chemical_list: D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen